Assessing LSAMs ability to account for changes in organ donation and transplant center behavior.

BACKGROUND: The Liver Simulated Allocation Model (LSAM) is used to evaluate proposed organ allocation policies. Although LSAM has been shown to predict the directionality of changes in transplants and non-used organs, the magnitude is often overestimated. One reason is that policymakers and researchers using LSAM assume static levels of organ donation and center behavior because of challenges with predicting future behavior. METHODS: We sought to assess the ability of LSAM to account for changes in organ donation and organ acceptance behavior using LSAM 2019. We ran 1-year simulations with the default model, and then ran simulations changing donor arrival rates (i.e., organ donation) and center acceptance behavior. RESULTS: Changing the donor arrival rate was associated with a progressive simulated increase in transplants, with corresponding simulated decreases in waitlist deaths. Changing parameters related to organ acceptance was associated with important changes in transplants, non-used organs, and waitlist deaths in the expected direction in data simulations, although to a much lesser degree than changing the donor arrival rate. Increasing the donor arrival rate was associated with a marked decrease in the travel distance of donor livers in simulations. CONCLUSION: We demonstrate that LSAM can account for changes in organ donation and organ acceptance in a manner aligned with historical precedent that can inform future policy analyses. As SRTR develops new simulation programs, the importance of considering changes in donation and center practice is critical to accurately estimate the impact of new allocation policies.

Barriers to Community-Based Eradication of Helicobacter pylori Infection.

Helicobacter pylori (HP) is a causative agent in gastric cancer (GC).1 In the United States, HP is more prevalent in racial and ethnic minorities, including African Americans, Asian Americans, Latinos, and immigrants, the same groups that are more likely to develop and die from GC.2 Although screening for HP is not presently performed in the United States, there are plausible benefits to doing so, because HP is considered a group 1 carcinogen by the World Health Organization, and its link to GC parallels that of human papilloma virus and cervical cancer.1 HP eradication as a means of preventing GC also fulfils the Wilson and Jungner criteria for a successful screening program, and literature has consistently demonstrated that HP eradication reduces GC risk and death from GC.3 In fact, in countries with a high burden of GC, HP eradication is considered primary prevention for GC. As such, targeted HP testing in the United States may reduce GC burden in high-risk groups.4 We evaluate the results of community-based HP testing in an at-risk, underserved population.

Upper helical reconstruction during aesthetic facelift procedure: a case report.

We present a case of a two-stage reconstruction of a traumatic right upper helix deformity using a random pattern layover skin flap in conjunction with an aesthetic facelift procedure. This serves to encourage reconstructive surgeons to be mindful about seeking opportunities to address additional patient concerns when appropriate and safe.

Reactive transport modeling of organic carbon degradation in marine methane hydrate systems.

Natural methane hydrate has often been observed in sand layers that contain no particulate organic carbon (POC), but are surrounded by organic-rich, fine-grained marine muds. In this paper, we develop a reactive transport model (RTM) of a microbially-mediated set of POC degradation reactions, including hydrolysis of POC driven by extracellular enzymes, fermentation of the resulting high-molecular weight dissolved organic carbon (HMW-DOC), and methanogenesis that consumes low-molecular weight dissolved organic carbon (LMW-DOC). These processes are mediated by two groups of microbes, fermenters and methanogens that are heterogeneously distributed in different lithologies, with the largest numbers of microbes in the large pores of coarse-grained layers. We find that the RTM can reproduce methane hydrate occurrences observed in two different geological environments, at Walker Ridge Site 313-H (Gulf of Mexico) and IODP Site U1325 (Cascadia Margin). We also find that microbes can degrade POC even if they are physically separated, as extracellular enzymes and DOC can diffuse away from where they are produced by microbes. Microbial activity is highest at relatively early times after burial at shallow depths and near lithological boundaries, where concentration gradients transport solutes to intervals that contain the most microbes.

Racial and Gender Disparities in Transplantation of Hepatitis C+ Hearts and Lungs.

BACKGROUND: Transplanting organs from hepatitis C virus (HCV)-infected donors into HCV-negative recipients has led to thousands of more transplants in the United States since 2016. Studies have demonstrated disparities in utilization of kidneys from these donors due to gender and education. It is still unknown, however, if the same disparities are seen in heart and lung transplantation. METHODS: We used Organ Procurement and Transplantation/United Network for Organ Sharing data on all isolated heart and lung transplants from November 1, 2018, to March 31, 2023, classifying donors based on their HCV nucleic acid test (NAT) result: HCV-NAT- vs HCV-NAT+. We fit separate mixed-effects logistic regression models (outcome: HCV-NAT+ donor) for heart and lung transplants. Primary covariates included (1) race/ethnicity, (2) sex, (3) education level, (4) insurance type, and (5) transplant year. RESULTS: The study included 26,108 adults (14,189 isolated heart transplant recipients and 11,919 isolated lung transplant recipients). A total of 993 (7.0%) heart transplants involved an HCV-NAT+ donor, compared to 457 (3.8%) lung transplants. In multivariable models among all isolated heart transplant recipients, women were significantly less likely to receive an HCV-NAT+ donor heart (odds ratio [OR]: 0.79, 95% confidence interval [CI]: 0.67-0.92, p = 0.003), as were Asian patients (OR: 0.52, 95% CI: 0.31-0.86, p = 0.01). In multivariable models among all isolated lung transplant recipients, Asians were significantly less likely to receive HCV-NAT+ transplants (OR: 0.31, 95% CI: 0.12-0.77, p = 0.01). CONCLUSIONS: There are disparities in utilization of heart and lungs from HCV-NAT+ donors, with women and Asian patients being significantly less likely to receive these transplants.

Implementing pragmatic clinical trials in hepatology.

Patients with chronic liver disease would benefit from pragmatic trial designs. A pragmatic trial seeks to inform clinical decision-making by providing evidence for the adoption of an intervention into real-world clinical practice. A trial's pragmatism is based on the efficiency by which it identifies, recruits, and follows patients, the degree to which the interventions and design mirror the usual clinical care, and the importance of the outcomes to the patients. We review the promise, trade-offs, and purpose of pragmatic trials in hepatology.

Regional Social Vulnerability is Associated With Geographic Disparity in Waitlist Outcomes for Patients With Non-Hepatocellular Carcinoma Model for End-stage Liver Disease Exceptions in the United States.

OBJECTIVE: This study was undertaken to evaluate the role of regional social vulnerability in geographic disparity for patients listed for liver transplantation with non-hepatocellular carcinoma (HCC) model for end-stage liver disease (MELD) exceptions. SUMMARY AND BACKGROUND: Prior work has demonstrated regional variability in the appropriateness of MELD exceptions for diagnoses other than HCC. METHODS: Adults listed at a single center for first-time liver-only transplantation without HCC after June 18, 2013 in the Scientific Registry of Transplant Recipients database as of March 2021 were examined. Candidates were mapped to hospital referral regions (HRRs). Adjusted likelihood of mortality and liver transplantation were modeled. Advantaged HRRs were defined as those where exception patients were more likely to be transplanted, yet no more likely to die in adjusted analysis. The Centers for Disease Control's Social Vulnerability Index (SVI) was used as the measure for community health. Higher SVIs indicate poorer community health. RESULTS: There were 49,494 candidates in the cohort, of whom 4337 (8.8%) had MELD exceptions. Among continental US HRRs, 27.3% (n = 78) were identified as advantaged. The mean SVI of advantaged HRRs was 0.42 versus 0.53 in nonadvantaged HRRs ( P = 0.002), indicating better community health in these areas. Only 25.3% of advantaged HRRs were in spatial clusters of high SVI versus 40.7% of nonadvantaged HRRs, whereas 44.6% of advantaged HRRs were in spatial clusters of low SVI versus 38.0% of nonadvantaged HRRs ( P = 0.037). CONCLUSIONS: An advantage for non-HCC MELD exception patients is associated with lower social vulnerability on a population level. These findings suggest assigning similar waitlist priority to all non-HCC exception candidates without considering geographic differences in social determinants of health may actually exacerbate rather than ameliorate disparity.

Transplant center variability in utilizing nonstandard donors and its impact on the transplantation of patients with lower MELD scores.

There is a subset of patients with lower MELD scores who are at substantial risk of waitlist mortality. In order to transplant such patients, transplant centers must utilize "nonstandard" donors (eg, living donors, donation after circulatory death), which are traditionally offered to those patients who are not at the top of the waitlist. We used Organ Procurement and Transplantation data to evaluate center-level and region-level variability in the utilization of nonstandard donors and its impact on MELD at transplant among adult liver-alone non-status 1 patients transplanted from April 1, 2020, to September 30, 2022. The center-level variability in the utilization of nonstandard donors was 4-fold greater than the center-level variability in waitlisting practices (waitlistings with a MELD score of <20). While there was a moderate correlation between center-level waitlisting and transplantation of patients with a MELD score of <20 ( p = 0.58), there was a strong correlation between center-level utilization of nonstandard donors and center-level transplantation of patients with a MELD score of <20 ( p = 0.75). This strong correlation between center-level utilization of "nonstandard" donors and center-level transplantation of patients with a MELD score of <20 was limited to regions 2, 4, 5, 9, and 11. Transplant centers that utilize more nonstandard donors are more likely to successfully transplant patients at lower MELD scores. Public reporting of these data could benefit patients, caregivers, and referring providers, and be used to help maximize organ utilization.

A randomized trial of mailed outreach with behavioral economic interventions to improve liver cancer surveillance.

BACKGROUND: Surveillance rates for HCC remain limited in patients with cirrhosis. We evaluated whether opt-out mailed outreach increased uptake with or without a $20 unconditional incentive. METHODS: This was a pragmatic randomized controlled trial in an urban academic health system including adult patients with cirrhosis or advanced fibrosis, at least 1 visit to a specialty practice in the past 2 years and no surveillance in the last 7 months. Patients were randomized in a 1:2:2 ratio to (1) usual care, (2) a mailed letter with a signed order for an ultrasound, or (3) a mailed letter with an order and a $20 unconditional incentive. The main outcome was the proportion with completion of ultrasound within 6 months. RESULTS: Among the 562 patients included, the mean age was 62.1 (SD 11.1); 56.8% were male, 51.1% had Medicare, and 40.6% were Black. At 6 months, 27.6% (95% CI: 19.5-35.7) completed ultrasound in the Usual care arm, 54.5% (95% CI: 47.9-61.0) in the Letter + Order arm, and 54.1% (95% CI: 47.5-60.6) in the Letter + Order + Incentive arm. There was a significant increase in the Letter + Order arm compared to Usual care (absolute difference of 26.9%; 95% CI: 16.5-37.3; p<0.001), but no significant increase in the Letter + Order + Incentive arm compared to Letter + Order (absolute difference of -0.4; 95% CI: -9.7 to 8.8; p=0.93). CONCLUSIONS: There was an increase in HCC surveillance from mailed outreach with opt-out framing and a signed order slip, but no increase in response to the financial incentive.

Upscaling DAC Hubs with Wind Energy and CO2 Mineral Storage: Considerations for Large-Scale Carbon Removal from the Atmosphere.

Continued fossil fuel emissions will increase CO2 concentrations in the atmosphere and could require removal of 10 Gt of CO2 per year or more to reach IPCC global climate goals. Large-scale construction of direct air capture (DAC) hubs to scrub CO2 from the atmosphere paired with geological storage is a prominent approach to potentially meet this target. We consider one location for theoretical scale-up of a DAC hub: the Kerguelen plateau in the Southern Indian Ocean which has high-potential renewable energy resources (wind) and large volumes of basalt rock for mineral storage. With consistent wind, previous studies indicate a hub in this location could collect approximately 75 Mt of CO2 annually, with conservative storage resources for 150-300 Mt of CO2 each year. Even with its immense wind and storage potentials, 14 Kerguelen-scale hubs would be needed to capture and store 1 Gt of CO2 per year. This brings into focus the important social, economic, and environmental trade-offs that must be considered in finding an acceptable balance between climate solutions, renewable energy requirements, and nature. Engaging public groups on these trade-off considerations will be crucial for gigaton scale-up of CO2 removal in just and responsible ways.

Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease: Synopsis of the Kidney Disease: Improving Global Outcomes 2022 Clinical Practice Guideline.

DESCRIPTION: The Kidney Disease: Improving Global Outcomes (KDIGO) 2022 clinical practice guideline on prevention, diagnosis, evaluation, and treatment of hepatitis C in chronic kidney disease (CKD) is an update of the 2018 guideline from KDIGO. METHODS: The KDIGO Work Group (WG) updated the guideline, which included reviewing and grading new evidence that was identified and summarized. As in the previous guideline, the WG used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to appraise evidence and rate the strength of recommendations and used expert judgment to develop recommendations. New evidence led to updating of recommendations in the chapters on treatment of hepatitis C virus (HCV) infection in patients with CKD (Chapter 2), management of HCV infection before and after kidney transplant (Chapter 4), and diagnosis and management of kidney disease associated with HCV infection (Chapter 5). Recommendations in chapters on detection and evaluation of hepatitis C in CKD (Chapter 1) and prevention of HCV transmission in hemodialysis units (Chapter 3) were not updated because of an absence of significant new evidence. RECOMMENDATIONS: The 2022 updated guideline includes 43 graded recommendations and 20 ungraded recommendations, 7 of which are new or modified on the basis of the most recent evidence and consensus among the WG members. The updated guidelines recommend expanding treatment of hepatitis C with sofosbuvir-based regimens to patients with CKD glomerular filtration rate categories G4 and G5, including those receiving dialysis; expanding the donor pool for kidney transplant recipients by accepting HCV-positive kidneys regardless of the recipient's HCV status; and initiating direct-acting antiviral treatment of HCV-infected patients with clinical evidence of glomerulonephritis without requiring kidney biopsy. The update also addresses the use of immunosuppressive regimens in such patients.

Patient randomised controlled trial of technology enabled strategies to promote treatment adherence in liver transplantation: rationale and design of the TEST trial.

BACKGROUND AND AIMS: Liver transplantation is a life-saving procedure for end-stage liver disease. However, post-transplant medication regimens are complex and non-adherence is common. Post-transplant medication non-adherence is associated with graft rejection, which can have long-term adverse consequences. Transplant centres are equipped with clinical staff that monitor patients post-transplant; however, digital health tools and proactive immunosuppression adherence monitoring has potential to improve outcomes. METHODS AND ANALYSIS: This is a patient-randomised prospective clinical trial at three transplant centres in the Northeast, Midwest and South to investigate the effects of a remotely administered adherence programme compared with usual care. The programme monitors potential non-adherence largely levering text message prompts and phenotypes the nature of the non-adhere as cognitive, psychological, medical, social or economic. Additional reminders for medications, clinical appointments and routine self-management support are incorporated to promote adherence to the entire medical regimen. The primary study outcome is medication adherence via 24-hour recall; secondary outcomes include additional medication adherence (ASK-12 self-reported scale, regimen knowledge scales, tacrolimus values), quality of life, functional health status and clinical outcomes (eg, days hospitalised). Study implementation, acceptability, feasibility, costs and potential cost-effectiveness will also be evaluated. ETHICS AND DISSEMINATION: The University of Pennsylvania Review Board has approved the study as the single IRB of record (protocol # 849575, V.1.4). Results will be published in peer-reviewed journals and summaries will be provided to study funders. TRIAL REGISTRATION NUMBER: NCT05260268.

Procurement of Pancreatic Tissue for Research From Deceased Donors Before vs After the CMS Final Rule in 2020.

This cohort study examines changes in research pancreas procurement from deceased donors before and after the Centers for Medicare & Medicaid Services (CMS) updated its Final Rule in November 2020.

Urgent need to mitigate disparities in federal funding for cancer research.

We evaluate National Cancer Institute (NCI) funding distribution to the most common cancers, considering their respective public health burdens, and explore associations between funding and racial and ethnic burden of disease. The NCI's Surveillance, Epidemiology and End Results, US Cancer Statistics database, and Funding Statistics were used to calculate funding-to-lethality (FTL) scores. Breast and prostate cancer had the first (179.65) and second (128.90) highest FTL scores, and esophagus and stomach cancer ranked 18th (2.12) and 19th (1.78). We evaluated whether there were differences between the FTL and cancer incidence and/or mortality within individual racial and ethnic groups. NCI funding correlated highly with cancers afflicting a higher proportion of non-Hispanic White individuals (Spearman correlation coefficient = 0.84; P < .001). Correlation was stronger for incidence than mortality. These data reveal that funding across cancer sites is not concordant with lethality and that cancers with high incidence among racial and ethnic minorities receive lower funding.

The SHELTER Trial of Transplanting Hepatitis C Virus-Infected Lungs Into Uninfected Recipients.

SHELTER is a trial of transplanting lungs from deceased donors with hepatitis C virus (HCV) infection into HCV-negative candidates (sponsor: Merck; NCT03724149). Few trials have reported outcomes using thoracic organs from HCV-RNA+ donors and none have reported quality of life (QOL). Methods: This study is a single-arm trial of 10 lung transplants at a single center. Patients were included who were between 18 and 67 y of age and waitlisted for lung-only transplant. Patients were excluded who had evidence of liver disease. Primary outcome was HCV cure (sustained virologic response 12 wk after completing antiviral therapy). Recipients longitudinally reported QOL using the validated RAND-36 instrument. We also applied advanced methods to match HCV-RNA+ lung recipients to HCV-negative lung recipients in a 1:3 ratio at the same center. Results: Between November 2018 and November 2020, 18 patients were consented and opted-in for HCV-RNA+ lung offers in the allocation system. After a median of 37 d (interquartile range [IQR], 6-373) from opt-in, 10 participants received double lung transplants. The median recipient age was 57 y (IQR, 44-67), and 7 recipients (70%) had chronic obstructive pulmonary disease. The median lung allocation score at transplant was 34.3 (IQR, 32.7-86.9). Posttransplant, 5 recipients developed primary graft dysfunction grade 3 on day 2 or 3, although none required extracorporeal membrane oxygenation. Nine patients received elbasvir/grazoprevir, whereas 1 patient received sofosbuvir/velpatasvir. All 10 patients were cured of HCV and survived to 1 y (versus 83% 1-y survival among matched comparators). No serious adverse events were found to be related to HCV or treatment. RAND-36 scores showed substantial improvement in physical QOL and some improvement in mental QOL. We also examined forced expiratory volume in 1 s-the most important lung function parameter after transplantation. We detected no clinically important differences in forced expiratory volume in 1 s between the HCV-RNA+ lung recipients versus matched comparators. Conclusions: SHELTER adds important evidence regarding the safety of transplanting HCV-RNA+ lungs into uninfected recipients and suggests QOL benefits.