Citations

Background and Aims: Cholangiocarcinoma (CCA) is a rare but aggressive malignancy with poorly understood genetic susceptibility. To date, genome-wide association studies (GWAS) investigating germline variants associated with CCA risk remain limited. We aimed to identify genetic risk loci for CCA and its clinical subtypes through comprehensive GWAS and post-GWAS analyses. Approach and Results: We conducted a GWAS of 2366 CCA cases and 11,750 controls of European ancestry. Genome-wide significant loci ( p <5×10 −8 ) were identified and further examined through fine-mapping, functional annotation, and HLA imputation. Subgroup analyses were conducted by CCA subtypes and primary sclerosing cholangitis (PSC) status. Cross-trait linkage disequilibrium score regression and Mendelian randomization were employed to investigate the shared genetic architecture and potential causal relationships with a diverse range of traits. We identified 1 new genome-wide significant variant, rs535777 (OR=1.44), near HLA-DRB1/DQA1 associated with CCA, and 2 variants associated with extrahepatic CCA: rs116224263 (OR=0.17) in LINC02506 at 4p15.1 and rs6914950 (OR=1.63) near HLA-DRB1/DQB1 . Stratified analyses revealed rs2395184 (OR=3.51) near HLA-DRA/DRB5 associated with PSC-related CCA, and rs142674434 (OR=2.98) in THSD7A at 7p21.3 associated with non-PSC-related CCA. HLA imputation uncovered new amino acid residues associated with disease risk. Cross-trait analyses identified shared genetic signals between CCA and anthropometric, lipidemic, lifestyle, and medical traits. Mendelian randomization supported putative causal associations for 12 traits with CCA or its subtypes. Conclusions: Our large-scale GWAS highlights new genetic variants and HLA-linked mechanisms underlying CCA susceptibility. Integrating multi-step post-GWAS approaches enhances understanding of CCA pathogenesis and may facilitate the development of risk biomarkers for early detection and precision prevention strategies.

Background: Biobanks often lack standard mechanisms to keep donors connected to their biospecimens, reflecting a broken feedback loop that compromises trust, engagement, and scientific progress. Decentralized biobanking empowers patients to track their donations throughout the research journey, supporting personalized feedback and research collaboration via a privacy-preserving blockchain network. This case study explores operational feasibility of implementing decentralized biobanking for a large breast cancer biobank at a US academic medical center. Methods: A mixed-methods case study of the groundwork, implementation, and stakeholder feedback for a real-world decentralized biobanking app pilot was conducted. Biobank members were recruited from February to April 2023. Operational feasibility was assessed via analysis of institutional stakeholder perspectives, pilot engagement, and de-bi app activity. Findings: Physicians and other biobank stakeholders surfaced challenges surrounding managing expectations, balancing empowerment with clinical and research workflows, and navigating power dynamics between patients, physicians, scientists, and leadership. A total of 1080 participants enrolled over 10 weeks, including nearly 10% of the biobank with about 4000 biospecimens. During the pilot, biobank enrollment increased 65% versus the prior year, and there were no biobank withdrawals during or within 1 year following the pilot ( p < 0.001 for both). The app, which facilitated biospecimen tracking and research engagement, was downloaded by 405 users. A total of 140 users tested the blockchain component, with 89% successfully claiming a nonfungible token representing their unique, immutable connection and access to donated biospecimens. Feedback was solicited to inform potential process improvements and risk assessments related to public relations, systems infrastructure, and ethical governance, illuminating next steps. Conclusions: We established operational feasibility for the first step toward decentralized biobanking, informed by requirements to manage expectations, workflows, and power dynamics. Our technical solution demonstrated robust participant engagement and compatibility with established biobanks, suggesting potential to build trust and align incentives and identifying next steps for communications, sustainability, and governance.

Objective: Multicancer Detection (MCD) tests, such as the GRAIL Galleri, offer a novel approach to cancer screening by detecting cancer-specific methylation patterns in cell-free DNA through a single blood sample. This study evaluated an 18-month implementation of MCD testing in a tertiary ambulatory internal medicine clinic. Patients and Methods: Between June 2022 and November 2023, 2244 asymptomatic (without symptoms attributed to cancer) patients underwent MCD testing. The study focused on operational workflows, patient and physician education, and diagnostic follow-up of positive results. Standardized materials, including electronic health record (EHR) workflows, FAQs, and diagnostic pathways, were developed to facilitate implementation. Challenges included managing false positives, patient anxiety, costs, and ethical considerations. Results: Of the 2244 patients tested, 17 (0.76%) had positive results, and 15 underwent further diagnostic evaluation. Cancer was confirmed in 11 (73.3%) patients, including cases of breast, colon, esophageal, lymphoma, ovarian, and pancreatic cancers. Four patients had no identifiable malignancy despite comprehensive work-up. Conclusions: MCD testing is feasible in routine clinical workflows, with 73% of positive cases yielding cancer diagnoses. While promising, further research is required to assess long-term outcomes, cost-effectiveness, and optimal implementation strategies of cancer interception in broader healthcare settings.

Background The Scientific Registry for Transplant Recipients (SRTR) publishes outcomes of all transplant centres in the USA two times a year. The outcomes are publicly available and used by insurance payers and patients to assess the performance of a programme. Poor performance can result in temporary suspension or termination of a transplant programme. The estimated 1-year survival hazard ratio (EHR) is an important metric publicly reported by the SRTR. Problem The EHR at our institution was 1.13, indicating a graft loss rate that was 13% higher than the national average. Methods/INTERVENTION We defined an improvement in this metric as achieving an EHR of <1.0. Our balance measure was maintaining similar liver transplant volumes and avoiding limiting access to transplant. Using a causality tree, we identified there was no ‘real time’ assessment of programme risk or objective metric to assess this. An affinity diagram was used to determine high and intermediate risk factors for mortality and graft loss and, using a REDCap form (a web application used to manage our database) to track actual and potential complications, we calculated a weekly ‘risk metric’ that was introduced at multidisciplinary selection conference meetings. Results We remeasured our EHR at each interval release of the SRTR outcomes and found it to be 0.98 and 0.65 after implementing the ‘risk metric.’ During the intervention period, annual liver transplant volume remained above the baseline measure. Conclusion By implementing a ‘risk metric’ to prospectively assess the risk of a low EHR at transplant selection committee meetings, we were able to reduce the EHR well below the national average without limiting access to liver transplants.

Background. Limited health literacy (HL) is associated with decreased kidney function and death in patients with chronic kidney disease. Less is known about the impact of HL on kidney transplant (KT) outcomes. The aim of this study was to examine the relationship between HL and KT outcomes, including rates of waitlisting, healthcare utilization, acute rejection, renal allograft function, renal allograft failure, and death. Methods. We performed a retrospective review of HL data previously collected at our center. HL was assessed in a convenience sample of consecutive, English-speaking patients age ≥18 y who were evaluated for KT at Mayo Clinic in Minnesota between June 2015 and March 2017 as part of a practice improvement feasibility project (n = 690). HL was assessed using the 4-item Brief Health Literacy Screening Tool modified for the outpatient KT evaluation process. The 4 items assess confidence completing forms, reading comprehension, and oral literacy. Results. Overall, 30.4% of patients had limited or marginal HL. Patients with limited or marginal HL were less likely than those with adequate HL to be waitlisted for KT (hazard ratio = 0.62 and 0.69, respectively), even after adjusting for age, marital status, body mass index, Charlson comorbidity index, or dialysis dependency. Patient HL was not associated with post-KT healthcare utilization, acute rejection, or renal allograft function. Patients with limited or marginal HL appeared to experience a higher risk of renal allograft failure and post-KT death, but the number of events was small, and the relationship was statistically significant only for marginal HL. Conclusions. Inadequate HL is common in KT candidates and independently associated with decreased waitlisting for KT. We observed no statistically significant relationship between HL and posttransplant outcomes in our cohort. Further efforts to improve communication in patients with inadequate HL may improve access to KT.

The efficacy and safety of a fluid‐filled intragastric balloon (IGB) for weight loss in patients with cirrhosis on the liver transplantation (LT) waiting list is unknown. We enrolled stable compensated patients with body mass index >35 kg/m2 and on the waiting list for IGB placement endoscopically for a maximum of 6 months. A total of 8 patients (7 men) aged mean ± SD, 56 ± 4.6 years with Model for End‐Stage Liver Disease–sodium (MELD‐Na) scores 14.1 ± 3.4 experienced weight reduction (146 ± 22.2 kg versus 127 ± 21.6 kg [P = 0.005] with IGB in place and 130 ± 24.6 kg [P = 0.014] at 6 months), with a total body weight loss of 12.2% ± 8.8% with IGBs in place and 10.9% ± 8.9% at 6 months. Body fat decreased from 48.6% ± 5.8% to 40.6% ± 6.4% (P = 0.001) and lean mass increased from 51.3% ± 6% to 59.4% ± 6.4% (P = 0.001). No change in MELD‐Na scores occurred (P = 0.770). Early balloon retrieval was attributed to accommodative symptoms (n = 2) and liver decompensation (n = 1). Mallory Weiss tears (n = 3), but no portal hypertensive bleeding, occurred. Liver decompensation and/or hepatocellular carcinoma (HCC) developed in 3 patients. A total of 4 patients with LT ± sleeve gastrectomy maintained overall weight loss. Of 4 patients who did not receive transplants, 2 experienced weight regain. IGB results in short‐term weight loss in patients with cirrhosis awaiting LT, with body fat loss without lean mass loss. Adverse effects were common. Decompensation and HCC did occur, with uncertainty of the relation to weight loss, and thus careful patient selection and close follow‐up are required.

Assessment of bone density is an important part of liver transplantation (LT) evaluation for early identification and treatment of osteoporosis. Dual‐energy X‐ray absorptiometry (DXA) is currently the standard clinical test for osteoporosis; however, it may contribute to the appointment burden on LT candidates during the cumbersome evaluation process, and there are limitations affecting its accuracy. In this study, we evaluate the utility of biomechanical analysis of vertebral images obtained during dual‐energy abdominal triple‐phase computed tomography (TPCT) in diagnosing osteoporosis among LT candidates. We retrospectively reviewed cases evaluated for LT between January 2017 and March 2018. All patients who underwent TPCT within 3 months of DXA were included. The biomechanical computed tomography (BCT) analysis was performed at a centralized laboratory (O.N. Diagnostics, Berkeley, CA) by 2 trained analysts blinded to the DXA data. DXA‐based osteoporosis was defined as a T score ≤−2.5 at the hip or spine. BCT‐based osteoporosis was defined as vertebral strength ≤4500 N for women or ≤6500 N for men or trabecular volumetric bone mineral density ≤80 mg/cm3. Comparative data were available for 91 patients who had complete data for both DXA and BCT: 31 women and 60 men, age 54 ± 11 years (mean ± standard deviation), mean body mass index 28 ± 6 kg/m2. Using DXA as the clinical reference, sensitivity of BCT to detect DXA‐defined osteoporosis was 83.3% (20/24 patients) and negative predictive value was 91.7%; specificity and positive predictive value were 65.7% and 46.5%, respectively. BCT analysis of vertebral images on triple‐phase computed tomography, routinely obtained during transplant evaluation, can reliably rule out osteoporosis in LT candidates. Patients with suspicion of osteoporosis on TPCT may need further evaluation by DXA.

Abstract Background Immunosuppressant therapeutic drug monitoring (TDM) usually requires outpatient travel to hospitals or phlebotomy sites for venous blood collection; however Mitra® Microsampling Device (MSD) sampling could allow self-collection and shipping of samples to a laboratory for analysis. This study examined the feasibility of using volumetric microsampling by MSD for TDM of tacrolimus (TaC) and cyclosporin A (CsA) in transplant patients, along with their feedback on the process. Methods MSD was used to collect TaC and CsA from venous (VB) or capillary (CB) blood. The MSDs were rehydrated, extracted, and analyzed using on-line solid phase extraction coupled to tandem mass spectrometry (SPE-MS/MS). We report an abbreviated method validation of the MSD including: accuracy, precision, linearity, carry-over, and stability using residual venous whole blood (VB) samples. Subsequent clinical validation compared serially collected MSD + CB against VB (200 µL) from transplant patients. Results Accuracy comparing VB vs. MSD+VB showed high clinical concordance (TaC = 89% and CsA = 98%). Inter- and intra-precision was ≤11.5 %CV for TaC and CsA. Samples were stable for up to 7 days at room temperature with an average difference of &lt;10%. Clinical validation with MSD+CB correlated well with VB for CsA (slope = 0.95, r2 = 0.88, n = 47) and TaC (slope = 0.98, r2 = 0.82, n = 49). CB vs. VB gave concordance of 94% for CsA and 79% for TaC. A satisfaction survey showed 82% of patients preferred having the capillary collection option. Conclusion Transplant patients favored having the ability to collect capillary samples at home for TaC/CsA monitoring. Our results demonstrate good concordance between MSD+CB and VB for TaC and CsA TDM, but additional studies are warranted.

INTRODUCTION: Learning styles among gastroenterology providers have not been reported and may have implications in improving continuing medical education (CME). This study aims to 1) evaluate learning styles among gastroenterology providers participating in a board review course, 2) assess self-reported burnout, and 3) determine if demographic information, practice style, or burnout was associated with specific learning styles. METHODS: Participants at the 2018 Mayo GI and Hepatology Board Review Course had the opportunity to participate in an anonymous, survey-based study evaluating learning styles and burnout. Demographic and practice information, reason for participating in the course, questions regarding burnout and callousness, and the Kolb Learning Style Inventory (KLSI) (v3.1, Korn Ferry Hay Group, Boston, MA) were collected. Associations between demographic data, burnout, and learning styles were assessed using Fisher’s exact test. RESULTS: A total of 71 of 230 participants elected to participate and 47 completed the KLSI. Median age range was 41-50 years, 31 (43.7%) were female, and 60 (84.5%) had MD or DO degree. All regions of the United States were represented and 4 participants were from outside of the US. Reasons for participation included new certification (12.7%), recertification (45.1%), not passing prior board certification (4.2%), and general knowledge (38%). Burnout was noted by 27 (38%), callousness by 19 (26.8%), and both by 9 (12.7%). Kolb learning styles were diverging in 27.7%, assimilating in 31.9%, converging in 27.7%, and accommodating in 12.8%. There were no associations with demographics, practice type or reason for taking the course with specific learning styles; however, more frequent markers of burnout were associated with the accommodating learning style (50% burnout only, 33% callous only, and 16.7% reporting both; P = .03). CONCLUSION: All learning styles are represented at the studied board review course and are dispersed throughout ages, sex, geography, and practice style. This highlights the importance of a transition from lecture-based CME to more varied education modalities. Indices of self-reported burnout are seen frequently in this cohort, and seem to have increased association with the accommodating learning style. Future study with more participants is needed to further understand learning styles and burnout in gastroenterology providers, with the aim of improving CME.