Publications

INTRODUCTION: Accurate, reliable means to obtain fresh viable clinically localised prostate cancer tissue do not exist. We developed a method in which bespoke 3D-printed moulds can be created for any prostate and allow for ex vivo sampling of magnetic resonance imaging (MRI)-visible, biopsy-proven cancer lesions. We sought to demonstrate the ability of our platform to obtain fresh viable prostate cancer tissue after robot-assisted radical prostatectomy (RARP).

METHODS: Inclusion criteria were a patient that underwent MR-fusion biopsy (UroNav, Philips) with a resulting biopsy proven Gleason Grade (GG) ≥ 2 target. STL files for prostate boundary and target regions of interest (ROI), created as part of fusion biopsy, were exported from the UroNav and imported into SolidWorks (Dassault), a solid modelling computer-aided design and engineering application. A macro within SolidWorks was then applied to create a material-optimised mould around the prostate with needle guides to allow for targeted sampling. The 3D mould was exported as an STL file and then 3D-printed on a Stratasys Fortus 250 MC 3D Printer. During RARP, the specimen is extracted, the seminal vesicles detached and the prostate is placed in the mould for biopsy. The biopsy cores are sent to pathology for analysis and compared to specimens from the initial biopsy.

RESULTS: Twelve patients with MRI-visible lesions and biopsy proven GGG ≥ 2 cancer underwent RARP. In 12 out of 12 patients, ex vivo biopsies performed with the 3D-printed mould yielded prostate tissue with cancer.

CONCLUSIONS: Our 3D-printed mould platform allows for ex vivo sampling of MRI identified and previously biopsied prostate cancer at the time of RARP. The native, cancerous tissue may then be used to advance further research. The potential applications for a platform that can reliably sample living prostate cancer tissue are numerous, including the ability to advance future cancer research as well as other solid-organ malignancies with targetable lesions.

BACKGROUND: Critical illness dramatically increases the demand for and consumption of leukocytes. This demand induces emergency hematopoiesis (EH) whereby the hematopoietic stem and progenitor cells in the bone marrow become activated and proliferate to increase leukocyte production. Recent studies in murine models of trauma demonstrate that trauma induces EH through IL-1-dependent production of G-CSF. We hypothesized that non-septic critical illness (NSCI) would similarly drive IL-1 and G-CSF- mediated EH in critically ill humans.

METHODS: Two independent prospective observational trials were conducted. Plasma cytokine levels were measured in a cohort of 55 critically injured trauma patients. G-CSF levels were measured on arrival and at 1, 6, 24, and 72 hours after arrival. Correlation between G-CSF levels and injury severity, length of stay, ICU length of stay and inflammatory cytokine levels were measured. Bone marrow was isolated from an independent cohort 6 non-septic critically ill organ donation candidates and 5 healthy donors. Hematopoietic stem and progenitor cells were measured by flow cytometry.

RESULTS: Critical injury induced a rapid and significant increase in plasma G-CSF levels, detectable within 1 hour of hospital arrival, with peak levels measured 6 hours after injury. G-CSF levels 1 hour after arrival correlated with injury severity, length of stay and ICU length of stay. 6 hour G-CSF levels correlated with ICU LOS. 6 hour G-CSF levels correlated strongly with 6-hour levels of IL-1β, IL-6 and IL-8. NSCI caused a significant increase in hematopoietic stem cells (HSC) and common myeloid progenitors and a significant decrease in multipotent progenitors and common lymphoid progenitors as compared to healthy controls.

CONCLUSIONS: Trauma induces a rapid increase in plasma G-CSF levels that is strongly correlated with plasma IL-1β, suggesting that as in murine models, IL-1 may be driving G-CSF production. As in mice, NSCI induced EH, characterized by expansion of the HSC cohort and a shift toward myelopoiesis. In critically ill humans these data suggest that sterile injury induces IL-1 and G-CSF mediated EH, recapitulating the murine finding.

Anorexia nervosa is a severe psychiatric disorder characterized by persistent food restriction and often excessive physical activity, implicating dysfunction in neural circuits governing motivation, reward, and behavioral persistence. The nucleus accumbens (NAc) is a central component of these circuits, yet synaptic and cellular adaptations within this region during anorexia-like states remain poorly defined. Using the activity-based anorexia (ABA) paradigm in adult female mice, we examined glutamatergic signaling and intrinsic neuronal properties in the NAc shell. ABA exposure produced rapid weight loss, reduced food intake, and progressively increased running-wheel activity. Biochemical analyses of NAc shell tissue revealed elevated membrane-associated GluA2 AMPA receptor protein. Consistent with this finding, whole-cell patch-clamp recordings from medium spiny neurons showed increased amplitude of spontaneous excitatory postsynaptic currents. ABA also enhanced intrinsic neuronal excitability, reflected by greater firing in response to depolarizing current injections. Together, these convergent biochemical and electrophysiological results demonstrate that ABA induces coordinated postsynaptic strengthening and increased intrinsic excitability in NAc shell medium spiny neurons. These adaptations suggest a sustained increase in accumbal output that may bias motivational circuit function and contribute to excessive activity and suppressed feeding during anorexia-like conditions, paralleling glutamatergic plasticity observed in other compulsive disorders, including substance use disorder.

OBJECTIVES: Air medical transport (AMT) improves survival for selected trauma patients. Improving AMT triage is limited by a lack of evidence and a standardized definition for which patients and circumstances may warrant AMT. Our objective was to develop a consensus-based definition of AMT need.

METHODS: We recruited a multidisciplinary, nationally representative panel with expertise in AMT from trauma surgery, anesthesiology, critical care, emergency medicine, and emergency medical services (EMS). Panelists were presented with criteria from the literature representing the potential for AMT need that included patient injuries, time-sensitive interventions, and system factors. Panelists voted over 4 rounds to refine and select (≥70% agreement) a final set of criteria using a web-based Delphi methodology, including potential criteria combinations.

RESULTS: A total of 32 of 45 (71.1%) invited panelists agreed to participate. From 66 initial criteria, panelists reached consensus on 18 patient factors, 6 time-sensitive interventions, 3 system factors, and 7 combinations of criteria. Two key themes emerged: the need for specialized care from air medical crews that may not be available from ground ambulance clinicians, as well as overall prehospital time-savings. After narrative feedback and refinement to eliminate redundant and overlapping criteria, an algorithm for AMT need was developed along with a decision flow diagram suitable for educational dissemination.

CONCLUSIONS: We developed a consensus-based definition of AMT need for trauma patients that can be operationalized for AMT triage. Further validation of this concept with patient outcomes and identifying implementation barriers will contribute to field deployment of a useful AMT triage tool for EMS clinicians.

Understanding the decision-making process of black-box neural networks is crucial for safe use of AI in high-stakes medical tasks such as histopathology. We present Adaptive Example Selection (AES), a prototype-based explainable AI framework that improves interpretability of deep learning models for mitosis detection. AES retrieves a sparse set of supporting and contradicting real-world prototype images to locally approximate the model's confidence surface with high fidelity ([Formula: see text]). The framework is integrated with a robust Faster R-CNN detector that demonstrates strong cross-tumor performance, for example achieving an F1-score of 0.84 on the Canine Cutaneous Mast Cell Tumor dataset. AES generates concise, case-specific explanations that faithfully capture local decision boundaries while linking predictions to interpretable exemplars. This enables clinicians to visualize model reasoning, assess uncertainty, and conduct contrastive analyses. Unlike prior methods focused on discrete class predictions, AES shows how similarity to mitotic and non-mitotic prototypes shapes graded confidence, enhancing transparency, trust, and practical adoption of AI-assisted mitosis detection in cancer diagnostics.

IMPORTANCE: The initial treatment by emergency medical services (EMS) significantly affects the outcomes for severely injured patients. Effective control of hemorrhage, proper administration of blood products, and adherence to traumatic brain injury guidelines can reduce morbidity and mortality after trauma. Additionally, the experience of prehospital clinicians in high-acuity nontrauma conditions is associated with improved outcomes.

OBJECTIVE: To evaluate the association of annual trauma patient volume and outcomes at the individual EMS clinician level.

DESIGN, SETTING, AND PARTICIPANTS: A secondary subset analysis was performed of the Linking Investigations in Trauma and Emergency Services (LITES) Task Order 1 study, a prospective observational cohort from 2017 to 2021. It includes severely injured patients, identified by an Injury Severity Score of 9 or higher, who were transported to a trauma center by 1 air and 1 ground agency. Data were analyzed from February 2023 to June 2024.

EXPOSURES: EMS crew mean 3-year adult trauma volume and 6-hour mortality and several EMS industry quality metrics.

MAIN OUTCOMES AND MEASURES: Patient-level risk-adjusted regression models were constructed to determine the association between EMS crew mean 3-year adult trauma volume and 6-hour mortality and several EMS industry quality metrics. The association of airway success metrics and procedural intubation volume was also assessed.

RESULTS: A total of 6769 patient-clinician interactions involving 359 clinicians and 3649 patients (median [IQR] age, 54 [33-70] years; 2490 male [68.2%]) were included in this study. For every increase of 5 adult trauma patients annually per crew, there was a 10% decrease in 6-hour mortality (adjusted odds ratio [aOR], 0.899; 95% CI, 0.811-0.996) and a 2.6% decrease in in-hospital mortality (aOR, 0.974; 95% CI, 949-0.999). In subgroup analyses including traumatic brain injury (aOR, 0.974; 95% CI, 0.949-0.999) and prehospital shock (aOR, 0.974; 95% CI, 0.949-0.999), volume was associated with reduced 6-hour mortality. Highest trauma volume among treating EMS crew members, nontrauma volume, and years of experience were not significantly associated with differences in mortality. Among EMS industry quality metrics, decreasing scene time (regression coefficient, -0.134; 95% CI, -0.191 to -0.077) was significantly associated with higher clinician volume. Intubation procedural volume was associated with greater odds of success without hypotension or hypoxia (aOR, 1.110; 95% CI, 1.040-1.190).

CONCLUSIONS AND RELEVANCE: Results of this cohort study suggest that higher patient volumes per EMS clinician were associated with lower early mortality rates after trauma. Exploring this association further is essential to optimize staffing, education strategies, and performance benchmarks.

OBJECTIVE: The objective of this study was to examine patient experiences with virtual (telephone and video) encounters in primary care and make recommendations to inform the broader adoption of virtual care.

DESIGN: A descriptive qualitative study using semi-structured interviews for data collection.

SETTING: Ontario, Canada.

PARTICIPANTS: Fifty-five primary care patients across Ontario, Canada, who had experienced at least one virtual (telephone or video) encounter with a healthcare provider in primary care, participated in semi-structured individual interviews conducted between 15 January 2021 and 22 March 2021.

RESULTS: With respect to patients' experiences with virtual care appointments, we identified the following seven themes: (1) Enhancing access, (2) Importance of patient-provider relationship, (3) Active communication and attunement, (4) Assuring privacy and confidentiality, (5) Shorter appointments, (6) Asynchronous technologies being underutilised and (7) Strengthening the future of virtual care. Despite the rapid adoption of synchronous virtual care, participants generally reported positive experiences. Virtual care enhanced access to care and was overwhelmingly supported for continued use. While new patient-provider relationships faced challenges, pre-existing, positive relationships thrived. Concerns about the shortness of virtual care appointments were reported.

CONCLUSIONS: Virtual care offers a promising modality for patients to experience care. Moving forward, primary care practices should consider expanding options for asynchronous virtual care, consider the length of virtual care appointments and offer patients greater choice in the modality of their care appointments.