Publications by Year: 2026

The BraTioUS (Brain Tumor Intraoperative Ultrasound) dataset [1] is a large-scale, multicenter, and publicly available collection of intraoperative ultrasound (ioUS) images acquired during glioma surgeries. Created through an international collaboration among six hospitals across five countries, BraTioUS comprises 1669 B-mode 2D ioUS images from 142 glioma patients collected between 2018 and 2023 using various ultrasound systems and acquisition protocols. It also includes masks supervised by experts of tumor segmentation from every ioUS image. BraTioUS addresses several limitations found in existing public datasets, such as lack of diversity in acquisition hardware, imaging protocols, and glioma types. The primary objective of this dataset is to be publicly available and accessible for the training and validation of machine learning models aimed at improving the interpretation and use of ioUS. The dataset's scale, quality, and heterogeneity make it a valuable resource for training and validating AI tools aimed at improving intraoperative decision-making and patient outcomes in glioma surgery.

Hepatocellular carcinoma (HCC) represents one of the leading contributors to cancer-related deaths, with the majority of patients diagnosed at stages where curative treatment is no longer possible. Combining stereotactic body radiotherapy (SBRT) with immune checkpoint inhibition (ICI) has gained increasing attention as a therapeutic approach. Beyond its ability to provide high local tumor control (LC), SBRT can provoke immunogenic tumor cell death, promote antigen release and presentation, and modulate the tumor microenvironment in ways that enhance systemic antitumor immunity. In this narrative review, we outline the scientific rationale for integrating SBRT with ICIs, discuss mechanistic and translational findings and summarize results from key clinical trials. The currently available data indicate a synergistic interaction, most notably reflected in improved survival and response rates. Nevertheless, variability in dose and fractionation schedules, treatment sequencing, and patient characteristics complicates interpretation. Well-designed prospective studies are needed to establish optimal protocols and identify predictive biomarkers to guide patient selection.

Intrarenal renin-angiotensin system (iRAS) activation has been implicated in tubulopathy in diabetic kidney disease (DKD), its underlying mechanisms remain unclear. Type 1 diabetic Akita mice and Akita mice with angiotensinogen (Agt) deletion in renal tubules (Akita AgtRT KO) and their respective controls were studied at 42 weeks. Akita mice exhibit increased AGT expression, oxidative stress, tubular cell size and luminal dilation in proximal tubules (PTs), while reduced in Akita AgtRT KO mice. Elevated senescence-associated β-galactosidase (SA-β-gal) activity and senescence-associated secretory phenotype (SASP) along with increased senescence marker p16 expression in distal tubules (DTs) were also observed in Akita mice, all normalized in Akita AgtRT KO mice. Human CKD/DKD datasets confirmed AGT positively correlated with CDKN2A/p16 expression. Akita mice also showed elevated NADPH oxidase 4 (NOX4) expression and mitochondrial cristae disruption in PTs, accompanied by significant oxidative DNA damage, renal inflammation, fibrosis and apoptosis cf. Akita AgtRT KO mice. In vitro, high glucose and angiotensin II (Ang II) triggered NOX4-mediated mitochondrial oxidative stress and dysfunction in proximal tubular (HK-2) cells. In addition, Ang II induced p16-dependent senescence in distal tubular (Madin-Darby canine kidney, MDCK) cells. Conditioned medium from senescent MDCK cells triggered epithelial-to-mesenchymal transition in HK-2 cells, which was reversed by losartan or N-acetylcysteine. These findings suggest that iRAS promotes tubulopathy in DKD through NOX4-induced mitochondrial oxidative stress and dysfunction in PTs and oxidative DNA damage-induced senescence in DTs, providing new therapeutic targets.

BACKGROUND: Variability in tacrolimus levels, measured with the Medication Level Variability Index (MLVI), and intrapatient variability (IPV) may be associated with graft outcomes in solid organ transplant recipients. However, the optimal method for measuring tacrolimus variability, the optimal timing for measurement, and intervention thresholds for pediatric kidney transplant recipients remain uncertain.

METHODS: Our retrospective study included 149 pediatric kidney transplant recipients who received tacrolimus for maintenance immunosuppression. MLVI and IPV were assessed across 3 post-transplant intervals: 2-week to 3-month; 3- to 6-month; and 6- to 12-month. Associations between MLVI or IPV and graft outcomes were analyzed using landmark survival analysis, adjusting for age at transplant, donor type, and transplant year. We used survival trees to identify optimal thresholds.

RESULTS: MLVI during 2-week to 3-month (aHR: 1.65; 95% CI: 1.08-2.52; p = 0.02) and 6-12-month intervals (aHR: 3.82; 95% CI: 1.39-10.5; p = 0.009) post-transplant was significantly associated with the risk of graft failure. Similarly, IPV during 2-week to 3-month (aHR: 1.63; 95% CI: 1.03-2.59; p = 0.04) and 6 to 12-month intervals (aHR: 2.22; 95% CI: 1.05-4.71; p = 0.04) was significantly associated with the risk of graft failure. IPV during a 2-week to 3-month interval was significantly associated with de novo donor-specific antibody (dnDSA) development (aHR: 1.38; 95% CI: 1.07-1.78; p = 0.02). We observed no significant associations between the 3- and 6-month interval and graft failure. Neither MLVI nor IPV during any interval predicted acute rejection.

CONCLUSIONS: IPV during the first 3 months was associated with dnDSA development. Both MLVI and IPV during the first 3 months and at the 6- to 12-month interval post-transplant were associated with increased risk of graft failure.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is the most common complication of prematurity, contributing to long term adverse respiratory outcomes that persist across the life course. However, it remains unclear how childhood opportunity impacts the underlying risk for developing BPD and post-discharge respiratory health, both of which may impact long term outcomes.

METHODS: Observational cohort of 845 children born very preterm (≤32 weeks), followed for post-prematurity respiratory disease. We derived childhood opportunity index (COI) from the census tract corresponding to each subject's address. Linear regression was used to identify the impact of COI on neonatal and childhood respiratory outcomes. In a secondary analysis, we examined differences in outcomes between races (White, non-White), across quartiles of COI.

RESULTS: Children residing in neighborhoods with lower COI were born at a significantly smaller birth weight, earlier gestation, and spent longer duration on mechanical ventilation (MV) in the NICU. No direct association was observed between COI and longer-term respiratory outcomes. Racial disparities in birth outcomes within COI quartiles became more pronounced at higher levels of opportunity. Longer duration of MV in the NICU was significantly associated with longer-term outcomes including increased hospital readmissions in early life and lower FEV1 and FVC % predicted in childhood.

CONCLUSION: Low COI is associated with longer duration of MV in the NICU, which itself is associated with increased healthcare utilization and reduced functional respiratory outcomes. Racial disparities in birth outcomes within similar neighborhood contexts demonstrate the need for targeted interventions to advance health equity in this population of vulnerable infants.

The topics of ethics and professionalism in anatomy have only recently gained prominence within the discipline, reflecting trends in medical and health professions education and an increasing awareness of societal expectations around the use of the dead. Educators in anatomy have had limited access to specific resources and no established communities of practice to support their understanding and teaching of these subjects. This article traces the journey of three anatomy educators who addressed this gap by developing dedicated educational resources for use in anatomy teaching. The initiative began in 2020 with the creation of a suite of freely available resources designed to provide accessible, engaging content for educators. Next, the project expanded to include quarterly webinars to facilitate dialog and knowledge exchange, as well as in person sessions at anatomical conferences that have fostered professional networking and collaborations. Over time, what began as a resource-driven initiative evolved into a broader movement. By 2025, this journey has culminated in the establishment of an active community of practice and the adoption of the moniker "Bioethics Unicorns" that has come to represent the initiative. This article reflects on the stages of this journey, the development of the resources and community of practice, and provides advice for those wishing to develop educational initiatives for education in their own communities.

BACKGROUND: Postoperative delirium is a frequent, serious complication triggered by various factors including systemic inflammation. Dexamethasone, an inexpensive anti-inflammatory steroid frequently administered for prophylaxis of postoperative nausea and vomiting, attenuates inflammation. We hypothesised that intraoperative dexamethasone administration is associated with a lower risk of postoperative delirium and assessed whether this is modified by the occurrence of its key side effect, hyperglycaemia.

METHODS: This retrospective cohort study analysed electronic health data from adult hospitalised patients undergoing non-cardiac, non-neurosurgical, and non-transplant procedures at Beth Israel Deaconess Medical Center (Boston, MA, USA) between January 1, 2008, and January 15, 2024. Patients with missing data, preoperative delirium or glucocorticoid use, mechanical ventilation for 72 h or more, and those not expected to survive without the procedure, were excluded. The primary exposure was intraoperative administration of intravenous dexamethasone. The primary outcome was 7-day postoperative delirium, identified by keyword-triggered manual discharge note reviews, diagnostic codes, and the Confusion Assessment Method. Hyperglycaemia was defined as peak 24-h postoperative blood glucose of more than 180 mg/dL. All analyses were adjusted for 43 patient-related and procedure-related variables.

FINDINGS: 92,832 patients were included (55.8% female, median age 60 years [IQR 48-70]), of which 41,983 (45.2%) received dexamethasone at a median dose of 8 mg (IQR 4-8). 2575 (2.8%) patients developed postoperative delirium. Emergency procedures accounted for 11,970 (12.9%) of cases. Intraoperative administration of dexamethasone was associated with a lower risk of delirium (adjusted odds ratio [aOR] 0.63, 95% CI 0.56-0.70; p < 0.001; adjusted absolute risk difference -1.1%, 95% CI -1.3 to -0.8). The exploratory four-way mediation analysis suggested a 10.4% greater dexamethasone-associated reduction of postoperative delirium risk when hyperglycaemia did not occur (no hyperglycaemia aOR 0.59, 95% CI 0.51-0.67; p < 0.001; hyperglycaemia aOR 0.85, 95% CI 0.68-1.07; p = 0.17).

INTERPRETATION: Intraoperative dexamethasone administration is associated with a lower risk of postoperative delirium, although this association was not evident in patients experiencing hyperglycaemia. Prospective studies should investigate the role of dexamethasone and optimised blood glucose control in delirium prevention.

FUNDING: Unrestricted philanthropic grant by Dr. J. and J. Buzen.

BACKGROUND: Surgical training relies heavily on subjective performance evaluation, which is resource-intensive and prone to assessor bias. Advances in digital surgery offer opportunities for objective assessment. While validity evidence for data-driven assessments increases, strategies for implementation in surgical training remain scarce. The aim of this study was to leverage stakeholder insights to develop an implementation framework for integrating data-driven surgical sabermetrics into training curricula.

METHODS: Structured workshops were conducted at two international surgical conferences (the Association of Surgeons of Great Britain and Ireland Congress, Edinburgh, May 2025 and the International Conference on Surgical Education and Training, Edinburgh, June 2025). Delegates participated in facilitated discussions, interactive polling, and group concept-mapping exercises to explore opportunities, delivery modalities, access rights, and contextualization for surgical performance metrics. Stakeholder perceptions were used to iteratively develop an implementation framework, balancing applicability to current training pathways and capturing the nuances of data-driven insights.

RESULTS: A total of 54 surgical trainees and trainers from 13 countries contributed. Opportunities centred on enhancing objective feedback, assessing non-technical skills, and tracking trainee progression. Video-based delivery and real-time feedback were prioritized for technical skills, dashboards were prioritized for non-technical and cognitive skills, and structured reports were prioritized for performance-based metrics. Supervising surgeons and training leads were identified as essential users of trainee data, with integration of multimodal data (for example surgeon physiology, case complexity) deemed essential for contextualization.

CONCLUSION: This study presents an implementation framework for surgical sabermetrics in training. The framework provides practical guidance on delivery, access, and integration of performance metrics, supporting data-driven feedback to optimize trainee development, advance surgical education, and improve patient outcomes.

PURPOSE: To describe an optical coherence tomography (OCT) finding that is highly prevalent in Danon disease.

METHODS: Retrospective observational case series at a single centre, combined with a systematic literature review of PubMed and EMBASE for genetically confirmed Danon disease patients with available macular OCT images. Fifty-two macular OCT scans from 29 genetically confirmed Danon disease patients (5 from our institution; 24 from 11 published studies) were included. For each patient, a single foveal-centred macular OCT scan per eye was selected for analysis. Two independent reviewers assessed images for the presence of outer nuclear layer (ONL) hyperreflectivity, with discrepancies resolved by consensus.

RESULTS: Evidence of ONL hyperreflectivity appeared in 39 macular scans (75%). Of the 13 scans without this finding (25%), 10 scans (19%) showed macular atrophy (including bull's-eye maculopathy cases) or cystoid macular oedema that obscured evaluation of outer retinal layers at the fovea, and two scans (4%) used colour-encoded OCT that prevented reliable evaluation of the ONL. In only one scan (2%), ONL hyperreflectivity was absent despite preserved foveal architecture and adequate image quality.

CONCLUSION: ONL hyperreflectivity is a highly prevalent OCT finding in Danon disease, most evident in young patients without advanced outer retinal atrophy. This feature may serve as a non-invasive finding of early retinal involvement. Longitudinal studies are warranted to confirm its prognostic value.