Citations

Foundation models are reshaping computational pathology by enabling scalable task-agnostic representations of histopathological whole-slide images (WSIs). Unlike earlier task-specific deep learning systems, pathology foundation models (PFMs) leverage massive whole-slide image repositories and self-supervised Vision Transformer architectures to achieve broad generalization and few-shot adaptability. Their evolution reflects a shift from weakly supervised approaches such as Clustering-Constrained Attention Multiple Instance Learning (CLAM) and hierarchical architectures such as Hierarchical Image Pyramid Transformer (HIPT) to large-scale efforts including foundation models, UNI, Virchow, Phikon, CONtrastive learning from Captions for Histopathology (CONCH), GigaPath, H-Optimus, Transformer-Based Pathology Image and Text Alignment Network (TITAN), and the Mayo Clinic Atlas. These models demonstrate impressive performance across diagnostic and prognostic benchmarks while also opening pathways for multimodal integration with genomics and clinical data. Yet significant barriers remain including inconsistent generalization across institutions, interpretability lagging behind clinical needs, and slow integration into routine laboratory workflows. Certain domains of anatomic pathology such as cytopathology, transplant pathology, frozen sections, and rare tumor subtypes remain particularly resistant to current models. Here, we review the development of PFMs, critically evaluate their strengths and limitations, and outline priorities for their safe and effective clinical translation. We argue that the next phase of PFM development will depend on rigorous benchmarking, pathologist-in-the-loop deployment, and multimodal fusion ensuring these models evolve from research tools into clinically robust systems.

Abstract The use of chimeric antigen receptor (CAR) T-cell therapy is increasing for adult B-cell acute lymphoblastic leukemia (B-ALL), with 3 CD19 CAR T-cell products commercially available. Several key clinical questions related to best practices for CAR T-cell administration in this population exist, and limited prospective randomized trials have been conducted to fill these knowledge gaps. Thus, to help guide clinical practice, we conducted a modified Delphi study to develop and validate consensus recommendations on the administration of commercially available CAR T-cell therapy for adults with B-ALL. Consensus panelists (n = 9) included principal investigators (PIs) from Real World Outcomes Collaborative of CAR T-Cell Therapy in Adult ALL (ROCCA) consortium sites and were selected based on expertise and CAR T-cell center volume. Final panel consensus recommendations were distributed for rating by the remaining PIs from ROCCA consortium sites, which served as the validation group (n = 27). Consensus topics included patient selection, bridging and pre–CAR T-cell leukemia staging, lymphodepletion, and CAR T-cell treatment setting, specific toxicity prevention and management, post–CAR T-cell response assessment and disease monitoring, and the role of consolidation and/or maintenance therapies after CAR T-cell therapy. Initially, 58 recommendation statements were evaluated for consensus. After 2 panel meetings, a total of 34 statements achieved consensus rating among the expert panel. After rating by the validation group, all but 1 recommendation statement continued to meet consensus, for a total of 33 consensus recommendation statements on the administration of CAR T-cell therapy in adult B-ALL.

Background Early-life dysbiosis associated with Cesarean section (C-section) delivery is increasingly recognized as a modifiable risk factor influencing short- and long-term health outcomes. This multidisciplinary expert consensus summarizes the clinical implications of C-section on infant gut microbiota. It proposes evidence-based strategies to mitigate these effects, with a focus on the critical window of the first 1,000 days of life. Methods A multidisciplinary panel of 16 pediatricians, neonatologists, pediatric gastroenterologists, and nutrition experts conducted a targeted narrative review of the literature to inform a structured expert consensus process and participated in an online structured consensus process. Seventeen consensus statements were developed and validated through discussion, expert voting, and commentary, supported by a targeted review of current scientific evidence. Results The expert panel reached consensus on the impact of C-section delivery on early microbiota composition and its clinical relevance, emphasizing that the rising prevalence of C-sections worldwide demands urgent attention. Experts unanimously emphasized the importance of exclusive breastfeeding as the primary strategy to support healthy microbiota development in infants born by cesarean section. When exclusive breastfeeding is not possible, evidence-based nutritional approaches, including selected prebiotics and probiotic strains with documented clinical efficacy, are recognized as promising alternatives for supporting microbial balance. Notably, the panel underscored that not all probiotics are equally effective and recommended shifting toward evidence-based strains shown to help restore gut dysbiosis in this population. Also, experts advocated for continuing microbiota-targeted support throughout the first 1,000 days of life, viewing this developmental window as a critical continuum rather than a limited early-life phase, while acknowledging the need for more long-term data. Additionally, education for healthcare professionals and parents about the long-term implications of C-section delivery was emphasized as a key enabler of the broader adoption of eubiosis-targeted strategies. Conclusions Optimizing microbial colonization in infants born by cesarean section requires a multifaceted approach that prioritizes breastfeeding, supports judicious use of evidence-based nutritional interventions when needed, and emphasizes education and continuity of care across early life. By aligning clinical practice with emerging microbiome science, early-life interventions may reduce dysbiosis-associated risks and improve long-term health outcomes.

Abstract Rationale Chronic thromboembolic disease (CTED), which is the result of persistent pulmonary vascular obstruction despite 3 months of anticoagulation, can present with significant functional limitations and exercise intolerance despite normal resting hemodynamics. These patients may experience functional impairment due to exercise-induced pulmonary hypertension, impaired stroke volume augmentation with exercise, ventilatory inefficiency, and/or preload insufficiency. Such exercise-induced pathophysiological abnormalities can significantly impair quality of life and contribute to poor long-term outcomes. Although balloon pulmonary angioplasty (BPA) has shown benefit in patients with chronic thromboembolic pulmonary hypertension (CTEPH), its role in CTED patients with normal resting hemodynamics remains uncertain. This systematic review and meta-analysis evaluated the efficacy of BPA in this population. Methods A systematic search of PubMed, Cochrane, Embase, and Scopus was performed from inception through March 1, 2025. A total of 763 studies were screened, of which 42 full-text articles were assessed: six met the inclusion criteria (four retrospective, two prospective), comprising 98 patients. Results Across the included studies, baseline mean values were 20.81 +/- 3.62 mmHg for mean pulmonary arterial pressure (mPAP), 3.49 +/- 1.42 Wood units for pulmonary vascular resistance (PVR), and 405.72 +/- 108.40 m for the 6-minute walk distance (6MWD). Balloon Pulmonary Angioplasty (BPA) was consistently associated with significant improvements in hemodynamic and functional outcomes; BPA reduced mPAP by 3.40 mmHg and PVR by 0.90 WU, while increasing 6MWD by 31.90 m. These changes were also statistically robust across studies, with pooled standardized mean changes (SMC) of -0.88 for mPAP (95% CI, -1.10 to -0.67; P < .05), -0.68 for PVR (95% CI, -0.87 to -0.49; P < .05), and 0.29 for 6MWD (95% CI, 0.13 to 0.45; P < .05). Study-level effect sizes for 6MWD ranged from 0.19 to 0.54 (Figure 1A). Functional improvements were further demonstrated by shifts in NYHA class distribution (Figure 1B). Conclusion BPA was associated with meaningful reductions in mPAP and PVR and significant improvements in functional capacity among patients with CTED. These results indicate that BPA could be an effective treatment for certain patients with CTED, though more research is necessary. This abstract is funded by: None

Abstract Rationale Chronic thromboembolic disease (CTED) is characterized by persistent pulmonary vascular obstruction due to unresolved thromboemboli despite at least three months of anticoagulation. Although resting hemodynamics often remain normal, affected patients frequently develop functional limitation due to exercise-induced pulmonary hypertension, ventilatory inefficiency, limited stroke volume augmentation, or preload insufficiency. Such exercise-induced pathophysiological dysregulation can significantly impair quality of life and contribute to poor long-term outcomes. Pulmonary endarterectomy (PEA) is an established treatment for Chronic Thromboembolic Pulmonary Hypertension (CTEPH), offering significant improvements in hemodynamics and survival. Its role in CTED, however, remains unclear. While CTED has traditionally been managed with anticoagulation and supportive therapy, emerging evidence suggests PEA may provide symptomatic and functional benefit in selected CTED patients. Given the ongoing uncertainty regarding the role of PEA in CTED, we performed a systematic review and meta-analysis to define its safety profile and clinical efficacy in this patient subset. Methods A systematic search of PubMed, Cochrane, Embase, Scopus, Web of Science, ClinicalTrials.gov, and Google Scholar was conducted from database inception to March 1, 2025. Of 2,244 records screened, 34 full-text articles were assessed, and seven met the inclusion criteria. Results Across the included studies, the pooled baseline mean values were 20.48 ± 3.03 mm Hg for mean pulmonary arterial pressure (mPAP), 2.83 ± 1.11 Wood units for pulmonary vascular resistance (PVR), and 397 ± 100.08 m for the 6-minute walk distance (6MWD). Pulmonary Endarterectomy (PEA) was consistently associated with significant improvements in hemodynamic and functional outcomes; PEA reduced mPAP by 3.58 mmHg (pooled Standardized Mean Change (SMC)=-1.03; 95% CI, -1.23 to -0.83; P < .05), PVR by 0.86 Woods units (pooled SMC=-0.86; 95% CI, -1.05 to -0.67; P < .05), while, conversely, increased 6MWD by 37.49 m (pooled SMC, 0.49; 95% CI, 0.32 to 0.67; P < .05). Study-level effect sizes for 6MWD ranged from 0.21 to 1.47 (Figure 1A). This clinical improvement is further reflected in the enhancement of the NYHA functional class, as illustrated in Figure 1B. Conclusion PEA was associated with significant reductions in mPAP and PVR, as well as a considerable improvement in functional capacity in patients with CTED, with robust results across multiple tests for bias, influence, and sensitivity analyses. These findings support PEA as a viable therapeutic option for selected patients with CTED, although further research is warranted. This abstract is funded by: None

Abstract Introduction Emergent endotracheal intubation in the intensive care unit (ICU) is a high-risk, time-sensitive procedure performed to maintain airway patency and ensure adequate oxygenation and ventilation, often complicated by hypotension, hypoxemia, or cardiac arrest. Successful outcomes depend on precise team coordination, communication, and situational awareness. Drawing inspiration from the demonstrated benefits of simulation-based cardiopulmonary resuscitation training in enhancing team performance, this study examines the feasibility of implementing in situ “mock intubation” in the ICU. The objective is to determine whether this approach can be seamlessly integrated into routine practice to improve teamwork, procedural readiness, and patient safety. Methodology A prospective interventional study was conducted in the medical ICU at Mayo Clinic Rochester over two months. ICU staff—including physicians, advanced practice providers (APP), nurses, and respiratory therapists—participated in eight scheduled 45-minute in situ mock intubation sessions integrated into routine clinical hours. Each session included five participants (one physician faculty, one physician trainee/APP, two nurses, and one respiratory therapist) and incorporated case-based scenarios requiring completion of the intubation and management of post-procedural complications. Structured debriefings followed each session to identify performance gaps, enhance team communication, and assess the educational value and feasibility of incorporating mock intubation into routine ICU practice. Results A total of eight mock intubations were conducted with 40 participants. Sessions were seamlessly integrated into the routine clinical workflow without disruption. Participants reported high satisfaction, unanimously agreeing that the sessions were valuable and should be continued. Feedback emphasized psychological safety and realism: “This offered a safe space to communicate,” one noted; another stated, “It’s important to practice where it’s easy to make mistakes,” and a third remarked, “Real-life experiences were brought into simulations.” These themes underscore participants’ desire for ongoing sessions and their perceived real-world relevance. Conclusion Mock intubation using in situ simulation provides a practical approach to training for emergent endotracheal intubation, enhancing team communication, coordination, and situational awareness in the ICU. This on-site format eliminates the need for off-unit scheduling and was well received by staff. The potential of in situ mock intubation to mirror the success of simulated cardiopulmonary resuscitation training highlights the importance of team-based procedural preparation in high-acuity environments. The intervention fosters procedural readiness, teamwork, and a culture of safety. Given its feasibility, clinical relevance, and positive reception, in situ mock intubation should be integrated into routine ICU practice as a team training tool for high-risk procedures. This abstract is funded by: None

Rationale: Pulmonary hypertension (PH) is a fatal disease characterized by a sustained elevated pulmonary vascular resistance that results in right heart failure. Despite therapeutic advances, no treatment provides disease progression reversion, resulting in poor long-term survival. Identifying new therapeutic targets for PH therefore requires a deeper understanding of its mechanisms. A defining feature of PH is pulmonary vascular remodeling, a result from excessive proliferation, migration, and apoptosis resistance of pulmonary artery smooth muscle cells (PASMC). SNAI1, a transcription factor regulating cell proliferation and differentiation during development and disease, has recently been implicated in endothelial dysfunction and endothelial-to-mesenchymal transition in PH. However, its role within PASMC remains unknown. Here, we aimed to define the contribution of SNAI1 in PASMC to the pathogenesis of PH. Methods: Normal human PASMC were exposed to normoxia (21% O 2 ) or hypoxia (3% O 2 ) for 72 hours. PASMC were also isolated from patients with or without PH. Cell proliferation and migration were assessed by EdU incorporation and wound scratch assays respectively. Mice were exposed to hypoxia (10% O 2 ) or Sugen5416/hypoxia (10% O 2 plus Sugen5416 20mg/kg, i.p., weekly) for 6 weeks. PH phenotype was characterized by right heart catheterization, right ventricle (RV) hypertrophy by Fulton index and pulmonary artery (PA) remodeling by H&E staining of lung tissues. Pharmacological blocker GN-25 was used to inhibit SNAI1 in vitro and in vivo. Results: SNAI1 expression was markedly increased in hypoxic PASMC and in PASMC from patients with PH. Hypoxia also upregulated HIF-1alpha, Vimentin, p-AKT, PCNA at the protein level in PASMC. EdU incorporation and migration rates were significantly higher in hypoxic cells as well as in PASMC isolated from PH patients compared with controls. In vitro, GN-25 (100 nM) abolished hypoxia-induced PASMC proliferation and migration. Right ventricular systolic pressure (RVSP), a surrogate measurement of PA systolic pressure, estimated mean PAP (mPAP), and RV contractility (RV-±dP/dtmax) were significantly increased in both PH models compared with controls. Additionally, Sugen5416/hypoxia-treated mice exhibited higher RVSP, mPAP and RV-±dP/dtmax compared to hypoxia-treated animals. The Fulton index (weight of RV vs. left ventricle and septum), was increased in both PH groups indicating development of RV hypertrophy in PH compared to control. PH mice lost body weight by 5-10%. Additionally, when Fulton index was normalized by body weight, RV hypertrophy was significantly higher in Sugen5416/hypoxia-treated mice compared with hypoxic animals. Lung tissues from PH mice exhibit PA hypertrophy (media remodeling) with some PA partially or completely occluded. Additionally, we detected protein upregulation of Snai1 and Vimentin in lung tissues of PH mice in both groups. Treatment of PH mice with GN-25 (20 mg/kg, daily, for the last 3 weeks under PH stimuli) in reversal experiments attenuated PH phenotype in both animal models by decreasing hemodynamic parameters, right ventricle hypertrophy and pulmonary vascular remodeling. Conclusions: Our findings identify a key role for SMC SNAI1 in the pathogenesis of lung vascular remodeling during hypoxia-induced PH. Inhibition of SNAI1 in PASMC may constitute a new therapeutic strategy for the treatment of PH. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Background The prevalence and clinical correlates of extra-aortic vascular disease in Marfan syndrome remain incompletely defined, and current surveillance strategies primarily target the thoracic aorta. Methods We conducted a multicentre retrospective cohort study of 783 patients with Marfan syndrome across three tertiary centres, with systematic chart and imaging adjudication to define aneurysm and dissection distribution. Results Extra-aortic aneurysms were identified in 32% of patients, most commonly involving the iliac, carotid and subclavian arteries. Extra-aortic dissections occurred in 5.2%. Extra-aortic aneurysms clustered strongly with markers of advanced aortic disease, including abdominal aortic aneurysm (adjusted OR 3.48), prior aortic dissection (OR 3.39) and extra-aortic dissection (OR 4.44), as well as age >40 years and male sex. Genetic confirmation status was not associated with extra-aortic aneurysm presence. Conclusions Extra-aortic vascular involvement is common in Marfan syndrome and closely linked to advanced aortic pathology. These findings support risk-stratified vascular imaging beyond the thoracic aorta in higher-risk patients.