Citations

Background: Hepatocellular carcinoma (HCC) has a poor long-term prognosis due to high recurrence and cirrhosis-related mortality, even after potentially curative treatments such as liver transplantation (LT), surgical resection, or ablation. This study aimed to identify factors associated with ≥10-year survival in HCC patients. Methods: A retrospective cohort study was conducted among HCC patients diagnosed between 2004 and 2022 using the National Cancer Database. Multivariable Cox regression was used to identify predictors of overall survival, and logistic regression was used to identify predictors of ≥10-year survival. Results: Among 249,600 HCC patients, 177,585 (71.2%) died within 5 years, 8613 (3.5%) died at 5–10 years, 54,988 (22.0%) were alive with <10 years of follow-up, and 8219 (3.3%) survived ≥10 years. LT, resection, and ablation were performed in 6.6%, 9.3%, and 11% of patients, respectively. Compared with ablation as the reference group, LT [adjusted odds ratio (aOR) 11.96, 95% confidence interval (CI): 11.27–13.29] and resection (aOR: 2.83, 95% CI: 2.57–3.08) increased the odds of ≥10-year survival, while non-curative treatments reduced the odds compared with ablation (aOR: 0.50, 95% CI: 0.47–0.55). Cox regression results were consistent with the logistic model, confirming the association. Decision tree analysis confirmed LT as the dominant determinant of long-term survival. Black individuals were associated with lower odds of ≥10-year survival (aOR: 0.88, 95% CI: 0.820–0.96) and decreased likelihood of receiving LT (aOR: 0.73, 95% CI: 0.55–0.96). Conclusions: LT offers the best chance of ≥10-year survival in HCC. Ensuring equitable access is essential, especially for Black patients who have lower transplant rates and worse outcomes.

ABSTRACT Pancreatic islet transplantation can restore endogenous insulin production and offers a potential cure for diabetes, but its clinical impact has been limited by the inability to preserve large numbers of functional islets for timely use. Cryopreservation could provide an on-demand supply, yet conventional methods cause ice formation, cell injury, and loss of insulin secretion. We developed CryoMesh, a vitrification platform that combines a low-toxicity cryoprotectant with a thermally conductive, biocompatible mesh to enable ultra-rapid cooling and rewarming for ice-free cryopreservation. This approach supports long-term, clinical-scale preservation of both human pancreatic and stem cell–derived islets while maintaining viability, architecture, mitochondrial integrity, and glucose-responsive insulin secretion. Human islets preserved for up to one year restored normoglycemia in diabetic mice, with complete recovery of function and no increase in immunogenicity or loss of potency. The combination of high viability, recovery, and functional preservation at clinical scale has not been achieved previously. By decoupling islet isolation and manufacture from transplantation, CryoMesh enables extended quality, potency, and safety testing, cost-effective batch production, and global banking and distribution. These capabilities remove a major barrier to curative cell therapy for diabetes and establish a generalizable strategy for preserving complex multicellular therapeutics. One Sentence Summary A clinical scale vitrification platform enables long-term banking of human pancreatic and stem cell–derived islets for transplantation.

Objective Meaningful assessments of how large language models (LLMs) incorporate clinical guidelines require large-scale testing over many queries. Here, we evaluate the prevalence of clinical guideline omissions and hallucinations in a large sample of diagnostic LLM outputs. Methods We used simulated case vignettes and zero-shot prompting to generate diagnostic outputs and rationales from GPT-4.1 and DeepSeek-V3. English case vignettes were created for hypercholesterolaemia and type-2 diabetes mellitus. Each vignette contained identical medical information, while sociodemographic characteristics varied in terms of sex, ethnicity and location. We calculated the prevalence of existing and hallucinated clinical guidelines in LLM outputs across disease, LLM and sociodemographic characteristics. Results We analysed a total of 12 197 LLM outputs, which quantifies three hazard areas: omissions (up to 97% for DeepSeek-V3 and 46% for GPT-4.1), hallucinations (up to 9%) and inconsistencies (guideline citation rate ranging from 0% to 78.39% across sociodemographic vignettes). Omission and hallucination rates were generally similar across vignettes with different sex or ethnicity data, yet were particularly sensitive to patient location. Discussion This study highlights significant variability in clinical guideline prediction across two different diseases, three different sociodemographic variables and two LLMs, even when the LLMs were instructed by identical prompts, establishing clinical guideline prediction in LLM outputs as a stochastic event. Conclusion The stochastic nature of LLMs creates a unique challenge for evidence generation and clinical deployment. Being able to measure and capture this stochasticity within high-quality research designs will be a prerequisite to advancing the responsible deployment of LLMs in healthcare.

Abstract Background Isocitrate dehydrogenase (IDH)-mutant gliomas are infiltrative tumors with limited treatment options at recurrence. Early studies suggest IDH inhibition has therapeutic activity. We evaluated clinical outcomes associated with IDH-1 inhibitor ivosidenib in recurrent IDH-1-mutant gliomas and molecular predictors of response. Methods We retrospectively analyzed adults treated with ivosidenib from January 2021 to August 2025 with predominantly recurrent, pretreated CNS WHO grade 2-4 astrocytoma IDH-mutant or grade 2-3 oligodendroglioma, IDH-mutant and 1p/19q codeleted. Prior anticancer treatments, toxicities, enhancement status at ivosidenib initiation, and genomic alterations were collected. The primary endpoint was progression-free survival (PFS); secondary analyses evaluated associations between PFS, genomic complexity, and CDKN2A/B homozygous deletion. Results Ninety-two adults, median age 43, were included: 61 astrocytomas and 31 oligodendrogliomas, mostly grade 2. Before ivosidenib, 69 had surgery, 64 chemotherapy, and 64 radiation. Median time from diagnosis to ivosidenib was 4.8 years, with median of two prior progressions. Median treatment duration was 5.8 months. Median PFS was 15.2, 4.6, and 2.1 months for astrocytoma grades 2-4, 14.0 and 6.9 months for oligodendroglioma grades 2-3. Increasing genomic complexity was associated with shorter PFS in univariate analysis. Patients without CDKN2A/B homozygous deletion had median PFS of 19.2 months. Two patients with homozygous deletion had median PFS of 0.6 months. Conclusions In this retrospective analysis of predominantly recurrent IDH-1-mutant glioma, ivosidenib was associated with longer PFS in lower-grade, non-enhancing tumors that received little or no prior anticancer treatment and less complex genomic profiles. These findings support a context-dependent benefit of IDH inhibition in recurrent disease.

Background/Objectives: Characterizing spinal cord multiple sclerosis (MS) lesions in MRI is critical for diagnosis, monitoring, and treatment evaluation. However, current automated approaches for lesion detection and segmentation are typically designed for specific MRI contrasts or acquisition sites, limiting their generalizability in real-world clinical settings where imaging protocols vary widely. This work proposes a robust multi-site, multi-contrast segmentation framework for spinal cord lesions. Methods: The segmentation model was trained and evaluated on a large-scale dataset comprising 4428 annotated images from 1849 persons with MS across 23 imaging centers, encompassing six MRI contrasts (T1w, T2w, T2*w, PSIR, STIR, and UNIT1) acquired at 1.5 tesla (T), 3 T, and 7 T. Results: Likert-type assessment performed by neuroradiologist ratings demonstrated superior generalization of the model compared to existing contrast-specific pipelines ( p < 0.01). Additional experiments evaluated robustness across spinal levels, acquisition resolutions, binarization thresholds, and quantitative evaluation on external labeled datasets. Conclusions: The proposed model can achieve accurate and reliable spinal cord MS lesion segmentation across heterogeneous MRI data, addressing a key barrier to clinical translation. The model is available in the Spinal Cord Toolbox v7.2 and higher. Code repository: https://github.com/ivadomed/seg-sc-ms-lesion-multicontrast

A new systems approach to diseased states and wellness result in a new branch in the healthcare services, namely, Personalized and Precision Medicine (PPM). To achieve the implementation of PPM concept, it is necessary to create a fundamentally new strategy based upon the recogni-tion of biomarkers and thus the targets to secure the grand future of drug design and drug dis-covery.Each decision-maker values the impact of their decision to use PPM on their own budget and well-being, which may not necessarily be optimal for society as a whole. It would be extremely useful to integrate data harvesting from different databanks for applications to provide more tai-lored measures for the patients resulting in improved patient outcomes, reduced adverse events, and more cost-effective use of the latest health care resources including diagnostic (companion ones or theranostics), preventive and therapeutic (targeted molecular and cellular) etc.Meanwhile, along with the impact of genomics and bioinformatics, pathology is the central specialty of PPM-related resources. Coupled with IT, the upgraded tools are ever more efficient and robust within clinical cancer settings. The latest algorithms may be able to identify and vali-date patterns which humans are not capable of quantifying easily, such as slight differences in textures or morphologies. In this sense, the impact of pathology allows a modular approach, as its various aspects are under development in several areas of PPM.Among the above-mentioned medical specialists involved in PPM, the pathologists play an im-portant and key role in the implementation and development of PPM-driven resources that are in the center of decision of many therapeutic choices. Recent advances in systems biology have tremendously affected the practice of precision pathology, gradually transforming it from a morphology-based into a precise molecular-based discipline. The enormous development of precision pathology research (integrating molecular OMICS and digital approaches) has raised great expectations concerning its impact on PPM aiming to custom-ize medical practice with a focus on the individual, based on the use of molecular tests, identifi-cation of genomic biomarkers, and development of targeted drugs.The precision pathology process introduces a new paradigm in pathology by leveraging digital imaging and IT technologies, and provides significant advancements in accuracy, efficiency, and collaboration. Among the latest innovations the precision pathology supported by digital tools, would dictate the implementation of high-resolution imaging, image analysis tools and integra-tion with molecular OMICS data. Integration of the approaches and resources will provide a true challenge for the future, requiring collaboration between oncologists, pathologists, biodesigners and bioengineers and remaining a challenge to precision cancer practice and profiled bioindustry.The latter requires precision pathologists highly trained in pre-analytic processes, tumor area mi-crodissection for tumor cell enrichment, methodology analysis and results. The in-depth study of molecular alterations in patients allows optimizing molecular diagnosis and selecting candidates for receive novel treatments against specific molecular targets. These patients would benefit from multidisciplinary approach and learning. In this sense, molecular diagnostics has a long tradition in pathology, especially in clinical one, where various OMICS-analyses of cancers are incorpo-rated into diagnostic and decision-making algorithms to secure a way where the pathologists con-tinue to play an essential role in developing and implementing molecular profiling tests in practice and communicate the results and their relevance with cancer practitioners.Cancer pathology is the central specialty of personalized and precision oncology (PPO). Meanwhile, the combination of comprehensive biobanking and the next wave of theranostic pathology technologies provides a natural, externally visible infrastructure that now allows pa-thology as a discipline – to engage directly with the biotechnology and pharma sector. We’re at an exciting junction in precision cancer pathology’s growth as a medical specialty, and pathology-driven biobanking is becoming both central to our core expertise and, even more importantly, a powerful enabler for many of the most promising growth areas of our discipline: PPM healthcare, clinical trials and drug development, theranostics, and functional assessment and monitoring of disease. In the context of these changes and challenges, the precision cancer pathology can play a fundamental role in both PPO-guided clinical practice and biodesign-driven cancer research.

ABSTRACT Background Chronic megacolon is an uncommon neurogastrointestinal disorder typically characterized by a persistent increase in colonic diameter. Methods Our aim was to identify adults with medical treatment‐refractory constipation without radiographic criteria for megacolon but with increased colonic compliance (refractory constipation with colonic hypercompliance (RCCH)), and to compare the colonic compliance in 7 identified patients with “RCCH” to colonic compliance in 10 patients with chronic megacolon by radiographic criteria (i.e., megacolon) and 40 healthy volunteers. After endoscopic placement, compliance of left or transverse colon was measured using a 10‐cm‐long infinitely compliant balloon connected to an electronically controlled rigid piston barostat. The barostat inflated the balloon from 0 to 44 mmHg in 4‐mmHg steps at 30‐s intervals to measure colonic compliance (pressure‐volume relationship). Eligibility criteria for inclusion were increased colonic compliance based on a functional assessment without meeting radiographic criteria for megacolon (i.e., RCCH). In the three groups, we compared colonic volumes at intra‐balloon pressure of 8, 16, 20, 32, and 44 mmHg, the pressure at half maximum volume, and the slope of the colonic compliance curve using ANOVA on ranks and Dunn's pairwise comparison test. Other features of colonic motility were documented. Results Colonic volumes at all pressures (8‐44 mmHg) and the pressure at half maximum volume were significantly greater in patients with megacolon and RCCH than in healthy controls ( p < 0.001 for both), but compliance was not significantly different between RCCH and megacolon. Conclusion A subset of patients with medically‐refractory chronic constipation has colonic compliance similar to that of patients with megacolon.