Faculty Bibliography

BACKGROUND:In expert centers, surgical resection rates of locally advanced pancreatic cancer (LAPC) following induction chemotherapy have increased beyond 20% with subsequent 25% five-year overall survival (OS). In the Netherlands, however, the historical low 8% LAPC resection rate compared with 23% in international expert centers reflects relative reluctance. Thereby, opportunities to achieve long-term survival in appropriately selected patients may be missed. This study evaluated whether nationwide implementation of international multidisciplinary best-practice for LAPC management is feasible while maintaining surgical safety benchmarks (in-hospital/30-day major morbidity <50% and mortality ≤5%). METHODS:A multidisciplinary protocol was designed in collaboration with four international experts and prospectively implemented nationwide within the Dutch Pancreatic Cancer Group (DPCG) (2022-2024). This observational cohort included consecutive patients diagnosed with LAPC, defined by DPCG criteria. Eligible patients had radiologically non-progressive disease after at least four months of multi-agent chemotherapy. All patients who underwent resection were included in this safety analysis. A predefined sub-group analysis included patients with National Comprehensive Cancer Network (NCCN) LAPC. Primary outcomes included in-hospital/30-day major morbidity (i.e., Clavien-Dindo grade ≥IIIa) and mortality. The expected number of resections was 53. RESULTS:Overall, 180 patients with LAPC underwent surgical exploration, of whom 155 (86%) underwent resection in 11 centers. Most (74%) resections were performed in the three LAPC surgical centers. Extended resections were performed in 77% of patients, including portomesenteric venous (60%), multivisceral (23%), and arterial (21%) resections. In-hospital/30-day major morbidity rate was 44% and mortality rate was 0.6%, both within pre-established safety benchmarks. Benchmarks were also reached for patients with NCCN LAPC (49% major morbidity, 2% mortality). CONCLUSION/CONCLUSIONS:Nationwide implementation of the international best-practice for LAPC was feasible with nearly three times more resections performed than expected, while morbidity and mortality remained well within predefined safety benchmarks.

BACKGROUND/UNASSIGNED:Differentiated service delivery (DSD) is increasingly available for HIV treatment. DSD has been shown to improve treatment retention, but DSD modalities incur higher costs than the clinic-based standard-of-care (SoC). We conducted a cost-effectiveness (CE) analysis to assess what DSD modalities, in what settings, would constitute an efficient use of limited HIV program resources. METHODS/UNASSIGNED:) to project HIV trends (incidence, prevalence, mortality), disability-adjusted life years (DALYs), and costs (2021 USD) arising from DSD versus SoC over 2022-2062 in four settings: South Africa, Malawi, Zambia, and a collective representation of African low- and middle-income countries (LMICs). We compared three DSD modalities: healthcare worker-managed community adherence groups (CAG), client-managed urban adherence group (UAG), and home ART delivery (HomeART). We calculated incremental cost-effectiveness ratios (ICERs) of DSD versus SoC from the health system perspective using country-specific CE thresholds, and performed one-way sensitivity analyses for key assumptions. RESULTS/UNASSIGNED:Community adherence groups (ICER: $274-$604/DALY averted) and UAG (ICER: $590-$720/DALY averted) were cost-effective for all country/model settings. HomeART was dominated by UAG in all settings. In nearly all settings, CE estimates of CAG were robust to uncertainty in DSD effectiveness (except Zambia), DSD costs, CE threshold (except South Africa), HIV-associated disability weights, and discount rates. Cost-effectiveness of UAG was highly sensitive to uncertainty in DSD effectiveness in all settings. CONCLUSIONS/UNASSIGNED:Community adherence groups and UAG can provide cost-effective alternatives to the clinic-based SoC in multiple African settings.

BACKGROUND:Neurological disorders affect approximately 3 billion people globally, yet clinical trial success is often hindered by poorly selected outcome measures, impacting trial design, compliance, and interpretation. Over the past 25 years, Core Outcome Sets (COS) have emerged as standardized tools to enhance outcome selection, ensuring comparability across studies and reflecting the priorities of both researchers and patients. Despite the success of COS initiatives in other fields, their development in neurology remains limited, leaving many trialists without disease-specific guidance. OBJECTIVES/OBJECTIVE:This study aimed to conduct an AI-assisted thematic synthesis of outcome domains from existing COS, with the goal of identifying structural patterns common to these sets and generating descriptive reference framework to inform future COS development. METHODS:COS-Neuro was developed using AI-assisted thematic framework analysis, complemented by expert review. A modified five-step thematic analysis was conducted without pre-determined codes: 1. Dataset Gathering - Data was collected from the COMET database, and COS domains for neurological disorders were coded. 2. Prompt Design & Testing - Large language models (LLMs), including ChatGPT 3.5, Google Gemini 1.5 Flash and Meta Llama-2-70b, were trialled, and prompts refined based on their outputs. 3. Thematic Analysis - LLMs categorised domains into core areas. 4. Human Refinement - Experts reviewed LLM-generated core areas and selected those most appropriate for further interpretation. 5. Clinical Validation - Experts validated the domains, core areas, and concepts. This approach integrated AI with expert oversight to develop an AI-descriptive thematic map of existing neurological COS. RESULTS:Utilising LLMs, particularly ChatGPT, an AI-assisted conceptual framework synthesising existing neurological COS was developed based on the analysis of 112 published COS. Through adaptation of the OMERACT model, the final framework comprised four overarching concepts, 13 core areas, and 75 domains identified through expert consensus. CONCLUSION/CONCLUSIONS:COS-Neuro provides a preliminary AI-assisted descriptive synthesis of existing neurological COS, organised using the OMERACT Filter 2.1 as a structural reference. This hypothesis-generating framework may serve as a foundational resource for future COS research and trial design, particularly in areas where no disease-specific COS exists. However, it requires prospective validation through disease-specific, multi-stakeholder consensus processes before clinical application. COS-Neuro also demonstrates the feasibility of AI-assisted thematic synthesis in this context and warrants evaluation in other specialties.

BACKGROUND AND AIMS/OBJECTIVE:Liver transplantation is a lifesaving, standard of care intervention for infants, children, and adolescents with liver tumors, inborn errors of metabolism, and irreversible liver disease caused by a wide spectrum of liver conditions. The American Association for the Study of Liver Diseases (AASLD) last published guidelines for the evaluation and selection of pediatric liver transplant candidates in 2014. This 2026 update aims to provide evidence-based recommendations that reflect current best practices and evolving clinical knowledge. METHODS:A multidisciplinary writing group of pediatric liver transplant experts and a medical librarian was convened by AASLD, with guidance by its Practice Guidelines Development Policy, and in collaboration with the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) and the American Society of Transplantation (AST). We conducted a systematic global literature review, formulated key clinical questions, and developed recommendations. Each recommendation was graded using the Oxford Centre for Evidence-Based Medicine framework and categorized by strength through a consensus voting process. CONCLUSION/CONCLUSIONS:This document provides clear, evidence-based guidelines on the transplant evaluation process and journey in infants, children, and adolescents. It outlines indications, contraindications, and barriers to transplantation based on robust, relevant published data. It offers best practices for pre-transplant assessment, organ allocation, and strategies to optimize survival, while allowing flexibility for individual clinical scenarios.

Diffusion magnetic resonance imaging (dMRI) is a non-invasive neuroimaging technique that enables in vivo assessment of white matter microstructure and is highly sensitive to tissue alterations associated with disease. Although substantial evidence links diffusion-derived metrics to underlying white matter tissue properties, the presence of complex within-voxel axonal configurations complicates their biological interpretation. Several methods have been proposed to assess diffusion properties of individual crossing axonal populations, but their validation and clinical applicability remain limited. Glaucoma, the second leading cause of blindness worldwide, is characterized by progressive loss of retinal ganglion cells and axonal damage in the optic nerve, leading to degeneration along the entire visual pathway. This degeneration includes secondary effects on fiber crossings within the optic chiasm, which are challenging to characterize with conventional diffusion methods. Here, we evaluated whether advanced diffusion metrics can detect microstructural alterations in these complex white matter configurations and whether these measures correlate with clinical markers of glaucoma severity. In this study, we evaluated 31 patients with asymmetric glaucoma and 31 healthy controls using advanced diffusion magnetic resonance imaging methods, including Diffusion Tensor Imaging, Constrained Spherical Deconvolution, multi-tensor fit via Multi-Resolution Discrete Search method, and Fixel-Based Analysis. We found significant differences of diffusion metrics in white matter tracts of the visual system, including the optic nerve, optic chiasm, optic tracts, and optic radiations. Moreover, diffusion metrics correlated with clinical ophthalmological parameters such as cup-to-disc ratio, visual field mean deviation, and retinal nerve fiber layer thickness. These findings support the use of advanced diffusion magnetic resonance imaging models as sensitive tools for detecting Wallerian degeneration and resolving complex white matter architecture in the human visual pathway, and demonstrate their utility to study other fiber-crossing regions throughout the brain.

While there have been great advancements in total knee arthroplasty (TKA) over the past 50 years, anterior knee pain (AKP) remains the most common concern among patients postoperatively. Despite exhausting evidence supporting no clinical difference in AKP with resurfaced vs. unresurfaced patellae in TKA, 87% of TKAs are resurfaced in the United States, compared with 2% in other countries. These large practice variations underscore a lack of consensus regarding the role of the patella and the approach to the anterior compartment of the knee in TKA. The aim of this review was to go beyond patellar resurfacing and describe the effects that surgical technique and implant design may have on AKP in current TKA.

BACKGROUND/UNASSIGNED:The practice of living donor kidney transplantation has evolved through innovations in logistics, technology, and clinical practice. In the United States, Good Samaritan donation, a historical label exclusive to nondirected donors, now incorporates voucher-based models. METHODS/UNASSIGNED:To determine how voucher-based nondirected living kidney donation has influenced the volume and practice of Good Samaritan living kidney donation in the United States, we analyzed living donor kidney transplants from 2000 to 2024 using data from the National Kidney Registry (103 transplant centers) and the Scientific Registry of Transplant Recipients. Temporal trends were derived by linear regression. RESULTS/UNASSIGNED:We identified 4662 Good Samaritan living donor kidney transplants, defined as historical nondirected and novel voucher-based nondirected donations. Of 2131 Good Samaritan living donor kidney transplants facilitated by the National Kidney Registry, donors had a median age of 43 y, were predominantly of White race (93%), and were women (60%). Recipients had a median age of 52 y and were racially and ethnically diverse (63% White, 14% Black, and 10% Hispanic). Annual Good Samaritan donation counts in the United States increased from 17 in 2000 to 439 in 2024, corresponding to a growth rate of 14.5%. Voucher-based nondirected donations increased from 2 in 2015 to 314 in 2024, comprising 72% of all Good Samaritan donations in that year. CONCLUSIONS/UNASSIGNED:The advent of voucher-based nondirected donation correlated with growth in Good Samaritan donation volume. Given the prevalence of voucher-based donations, connecting local kidney paired donation practices to voucher-based nondirected donation may improve access to and participation in living kidney donation.

Over half of dementia cases remain undiagnosed, with persistent disparities across racial, ethnic, and socioeconomic groups. Dementia care navigation (DCN) has demonstrated value in post-diagnosis settings. If implemented earlier, DCN could address diagnostic delays and care gaps. We define the diagnostic window as the period from initial symptom awareness through diagnosis and early care planning. Drawing on deliberations from the Alzheimer's Association Dementia Care Navigation Roundtable, we present a pre-diagnosis DCN framework organized across six domains and describe navigator roles across three phases: pre-evaluation, diagnostic assessment, and immediate post-diagnosis and transition. We address special considerations, including people without a care partner and those with unmet care needs. The framework complements federal initiatives such as the Guiding an Improved Dementia Experience (GUIDE) Model and the National Alzheimer's Project Act and identifies existing reimbursement pathways for pre-diagnostic navigation activities. Generating evidence to refine these models across diverse settings will be essential to inform policy action and system-level integration.