Citations

ABSTRACT Periprosthetic joint infection (PJI) is a devastating complication of total joint arthroplasty that can be challenging to diagnose and treat. Neutrophils are a prominent feature in PJI, with neutrophil extracellular traps (NETs) known to be present; little is known, however, about the physiology of PJI-associated NETs. Here, the proteomes of PJI and non-infectious arthroplasty failure (NIAF), analyzed using liquid chromatography tandem mass-spectrometry (LC-MS/MS) and proximity extension assay (PEA)-based profiling of fluids derived from sonication of arthroplasty components removed from patients who had undergone revision arthroplasty, were compared, with a focus on NET formation. In addition, in vitro effects of synovial fluid components on Staphylococcus aureus- induced NET formation were characterized. LC-MS/MS (PJI n = 85, NIAF n = 26) and PEA (PJI n = 95, NIAF n = 39) showed NET formation and neutrophil degranulation to be associated with PJI, with the complement cascade and platelet activation pathways identified as potential contributors. In vitro studies showed delayed NET formation in artificial synovial fluid compared to standard cell culture media conventionally used to evaluate NETs. Together, these results demonstrate the presence of NETs in PJI, identify potential pathways involved in PJI-associated NETosis, and point to an influence of synovial components on NET formation during PJI. IMPORTANCE Periprosthetic joint infection (PJI) is a major complication of joint replacement, placing a significant burden on patients and the healthcare system. Our research reveals that neutrophils and their antimicrobial “traps” are dominant features of the immune response at the infection joint site. Importantly, we found that the unique environment of the joint delays the formation of these traps, potentially contributing to the pathogenesis of PJI. By establishing a new experimental platform tailored for the infected joint, this work provides a foundational platform for probing these mechanisms and supports the development of improved diagnostic and therapeutic strategies.

Background : Diabetic-foot osteomyelitis (DFO) is a severe complication of diabetic-foot ulcers associated with delayed healing, amputation, and increased mortality. Machine learning (ML) has increasingly been explored for diagnosis and clinical decision-making in diabetic-foot care; however, the current evidence specific to DFO has not been systematically synthesized. Methods : We performed systematic searches of MEDLINE, Embase, Scopus, and Web of Science for studies published between January 2000 and May 2026. Studies that developed or evaluated ML models for DFO diagnosis, prediction, or outcomes were included. Data extraction was performed using the CHARMS framework, reporting followed PRISMA 2020 and TRIPOD-SRMA recommendations, and methodological quality was evaluated using PROBAST + AI. Due to considerable heterogeneity, narrative synthesis was performed. Results : A total of 10 studies published from 2022 to 2026 met the inclusion criteria. Five studies developed or evaluated ML models with a direct DFO diagnostic endpoint, one additional study evaluated model explainability, and four evaluated complementary DFO-relevant diabetic-foot applications. Reported discrimination ranged from 0.879 to 0.998, but comparisons were limited by differences in clinical endpoints, reference standards, input modalities and validation strategies. Only one direct DFO model was externally validated, and no study developed a multimodal model combining clinical and imaging data. Conclusion : Current evidence is limited by heterogeneous methodologies, limited external validation, and inconsistent reporting despite promising discrimination reported by several models. Future studies should evaluate whether multimodal models integrating clinical and imaging data provide incremental value over unimodal approaches, with external validation, calibration, and clinical utility assessment before clinical implementation.

ABSTRACT Persistent gaps in anatomical knowledge among incoming residents have raised concerns about clinical preparedness, especially in surgical and interventional disciplines. Conventional anatomy instruction and limited cadaveric exposure and learning opportunities in medical curricula have prompted calls for innovative, clinically focused anatomical curricular integration in clinical training. This article describes the development, implementation, and impact of a tailored Year 4 Clinical Anatomy Elective in the Department of Clinical Anatomy at Mayo Clinic, designed to reinforce competency in clinically relevant anatomical understanding and support learners' perceived preparedness during transitions to residency. A 4‐week elective was designed for fourth‐year medical students interested in pursuing a specific residency program. The course was personalized for students' clinical interests and incorporated fresh tissue dissection, simulation, procedural skills training, and imaging using an immersive learning platform. The elective was structured within the experiential learning model using a guided, self‐directed format within a multicapability laboratory and instructional environment, grounded in constructivist theory. A 5‐year review of elective records and informal thematic analysis of student feedback were conducted. Most participants pursued surgically related specialties, with orthopedic surgery being the most common. Exploratory thematic analysis identified six core themes: Professional Identity Formation, Educational Benefits, Learning Challenges, Connection to Clinical Practice, Patient Care Implications, and Future Preparation and Transferability. These students perceived gains in areas aligned with ACGME milestones: increased confidence, greater preparedness for residency, and improvement in their ability to apply anatomical knowledge in clinical settings. This perception may be indicative of lifelong learning and early educator identity formation. A specialty‐specific, clinically integrated anatomy elective may support learners' perceived preparedness for residency, reinforce clinically relevant anatomical understanding, and support the development of educational and professional competencies. Such targeted interventions may help address perceived gaps in anatomical preparedness during the transition to residency and contribute to postgraduate training within a competency‐based medical education framework.

Background: Incidental thyroid nodules (ITNs) detected on nonthyroid imaging contribute to thyroid cancer overdiagnosis, largely through downstream evaluation initiated by thyroid ultrasound (TUS). However, TUS follow-up rates for ITNs and their drivers in routine practice remain unclear. We quantified TUS utilization after ITN detection and identified patient, imaging, nodule, and reporting factors associated with this first step in the diagnostic cascade. Methods: We conducted a retrospective cohort study of adults without prior thyroid disease who underwent imaging that incidentally captured the thyroid at Mayo Clinic sites (2017–2023). A validated natural language processing pipeline identified ITNs and extracted nodule characteristics from radiology reports across multiple imaging modalities. The main outcome was the rate of TUS within 180 days after ITN detection. Clinical outcomes, including thyroid biopsy, thyroidectomy, and thyroid cancer diagnosis, were compared between patients who underwent TUS and those who did not. Factors associated with TUS utilization were assessed using multivariable logistic regression with penalized variable selection. Results: Among 115,683 patients who underwent thyroid-capturing imaging, 8426 (7.3%) had an ITN. These patients were predominantly female (64.6%) and White (89.7%), with a mean age of 61.7 years (standard deviation 15.2). Most nodules were detected on computed tomography (80.8%), most commonly from chest imaging (52.3%). Overall, 1677 patients with ITNs (19.9%) underwent TUS. In multivariable analysis, TUS use was independently associated with higher body mass index (odds ratio [OR], 1.20 per 10-unit increase; confidence interval [CI] [1.08–1.33]), nodule size ≥1.5 cm (OR, 1.79; CI [1.52–2.10]), and a radiologist recommendation (OR, 2.51; CI [2.12–2.98]), whereas older age was associated with lower odds of TUS (OR, 0.89 per 10-year increase; CI [0.84–0.93]). Patients undergoing TUS had higher rates of thyroid biopsy, partial thyroidectomy, and total thyroidectomy compared with those without it. All detected thyroid cancers (103 cases) occurred in the TUS group, representing 6.1% of that cohort. Conclusions: One in five patients with ITNs underwent TUS, representing a critical gateway to downstream diagnostic procedures and thyroid cancer detection. Factors associated with TUS utilization highlight opportunities to better define appropriateness of ultrasound after incidental nodule detection and to reduce unnecessary testing and treatment.

Abstract Neuroanatomy remains a core competency in neurosurgical training, particularly in skull base education, where learners must integrate three‐dimensional spatial understanding, radiologic correlation, and stepwise procedural knowledge. Cadaveric dissection remains foundational, but adjunctive digital tools may strengthen repeated visualization and anatomical review. We describe the educational rationale and implementation of integrating stereoscopic teaching, a stepwise digital application, photogrammetry, and virtual reality within an established neurosurgical skull base curriculum. Within the Mayo Clinic cranial base course embedded in a broader longitudinal curriculum, four postgraduate year 4 neurosurgery residents participated in transcranial and endoscopic cadaveric dissections supported by stereoscopic lectures, workstation‐based tablet guidance, and immersive review using photogrammetry, virtual reality, and computed tomography/magnetic resonance imaging correlation. The integrated design aligned these modalities with course objectives in anatomical landmark recognition, operative corridor planning, radiologic‐anatomic translation, and stepwise procedural rehearsal. The educational contribution of this model lies in the intentional integration of digital adjuncts around cadaveric dissection rather than in a single technology alone. This multimodal sequence may support spatial understanding, procedural preparation, and competency‐oriented skull base training while extending review beyond the laboratory. Current evaluation is best interpreted as preliminary program evaluation rather than definitive learner‐outcome evidence. This model may offer a transferable approach for programs seeking to complement cadaveric education with emerging digital tools and provides a basis for future prospective evaluations using multiple low‐stakes assessment data points across the broader curriculum.

BACKGROUND AND OBJECTIVES: Pediatric large-volume brain arteriovenous malformations (AVMs) carry a substantial lifelong hemorrhage risk, neurological symptoms, and treatment morbidity. Single-session stereotactic radiosurgery (SRS) is often unsuitable due to constraints on dose-volume toxicity. Volume-staged SRS (VS-SRS) enables sequential dosing of large nidus volumes, potentially enhancing safety while maintaining efficacy. Evidence in children remains limited. We aimed to evaluate outcomes of VS-SRS for large AVMs in pediatric patients. METHODS: A multicenter retrospective cohort was assembled from 21 centers, including patients aged younger than 21 years treated with VS-SRS for AVMs >10 cm 3 . Clinical and radiological end points included obliteration, hemorrhage, and permanent symptomatic radiation-induced changes (RIC). RESULTS: A total of 103 patients were included (median age 14 years; IQR, 12-17). The median nidus volume at first stage was 18.2 cm 3 (IQR, 12.3-25.6). Median prescription dose per stage was 17 Gy (IQR, 16-18). The median clinical follow-up from the first stage was 57.5 months (IQR, 25-138). Obliteration occurred in 42 of 103 patients (40.8%), with actuarial rates of 6.9% (95% CI: 2.8-14) at 3 years and 29% (95% CI: 20-39) at 5 years. Hemorrhage occurred in 17 of 103 patients (16.5%) during follow-up, and permanent RIC was observed in 9 of 103 patients (8.7%). CONCLUSION: VS-SRS is a reasonably safe, selected option for pediatric large-volume AVMs when microsurgical or endovascular cure is not feasible or prudent. Delivering ≥17 Gy per stage while limiting each treatment volume to <15 cm 3 supports durable nidus control with acceptable toxicity. VS-SRS represents a key modality in multidisciplinary management of this historically difficult-to-treat population.

OBJECTIVE Ruptured, large pediatric arteriovenous malformations (AVMs) pose a significant management challenge due to high rerupture risk and the morbidity of conventional treatments. Volume-staged stereotactic radiosurgery (VS-SRS) has emerged as an alternative; however, evidence for its use in this specific population is limited. This study aimed to evaluate the long-term efficacy and safety of VS-SRS for ruptured, large AVMs in a dedicated pediatric cohort. METHODS This international, multicenter, retrospective cohort study from 21 centers analyzed outcomes for 42 pediatric patients (age < 18 years) with previously ruptured, large AVMs treated with VS-SRS. The primary outcome was complete AVM obliteration, and secondary outcomes included post-SRS hemorrhage, radiation-induced changes (RICs), and favorable outcome. Favorable outcome in this study was defined as obliteration without post-SRS hemorrhage or permanent RIC. RESULTS At the initial SRS, the median patient age was 14.5 years, and the median AVM volume was 15.0 cm 3 ; most AVMs were high grade (Spetzler-Martin grades IV and V). With a median follow-up of 41.5 months, complete AVM obliteration was achieved in 21 patients (50.0%). The cumulative obliteration rate was 37% at 5 years and 56% at 10 years. Patients with a nidus volume of ≤ 10 cm 3 had significantly higher cumulative obliteration rates than those with a nidus volume > 10 cm 3 (log-rank test, p = 0.021). Similarly, patients treated with a prescription dose > 17 Gy showed significantly higher cumulative obliteration rates compared to those treated with a dose ≤ 17 Gy (log-rank test, p = 0.012). The cumulative 5-year incidences of hemorrhage and RICs following VS-SRS were 19% and 7%, respectively. In multivariable analysis, only larger total AVM volume was an independent predictor of a lower likelihood of favorable outcome (hazard ratio 0.89, 95% CI 0.80–0.99; p = 0.036). CONCLUSIONS In this multicenter pediatric cohort, VS-SRS for ruptured, large AVMs provides a reasonable chance of long-term obliteration, but generally acceptable risks of post-SRS hemorrhage and RICs exist. VS-SRS should be considered as an option for pediatric patients with large, ruptured AVMs.

Background: There is growing support for high-efficacy disease-modifying therapy (DMT) in multiple sclerosis (MS), but escalation (ESC) approaches remain common. Objective: To describe decision-making in a pragmatic trial of early high-efficacy treatment (EHT) versus ESC. Methods: DELIVER-MS is a multi-center, pragmatic, randomized controlled trial (RCT) with a parallel observational study (OBS), which enrolled treatment-naïve people with RRMS in 31 UK/US sites. Primary outcome was as follows: 36-month brain volume loss according to initial treatment approach (EHT vs. ESC). Stepwise multivariable logistic regression was used to predict participation in RCT versus OBS and choice of EHT versus ESC within the OBS cohort. Results: In total, 816 people with MS were enrolled. Participants declined randomization due to preference for a particular DMT (85%), efficacy concerns (20%), and safety concerns (9%). RCT versus OBS participation was associated with lower relapse rate ( p = 0.043) and greater brain parenchymal fraction ( p = 0.002). Among 374 in the OBS cohort, 125 (33%) chose ESC and 249 (67%) chose EHT. People commencing EHT had higher education attainment ( p < 0.001) and relapse rate ( p = 0.025). Conclusion: Baseline DELIVER-MS data demonstrate that participants with milder disease are more likely to participate in RCT. The choice of EHT versus ESC was associated with demographic factors and disease activity. Clinical trial registration: NCT03535298

Background: The role of venous Doppler ultrasound in assessing venous congestion in the setting of post-lung transplantation surgery is unknown. We performed a feasibility study on the use of venous Doppler ultrasound in the immediate post-operative period after lung transplantation in a retrospective, single-center observational evaluation. Patients had at least two venous congestion Doppler ultrasound exams involving interrogation of IVC diameter, hepatic vein, portal vein and renal vein Doppler assessments. Results: A total of 9 patients were included in our study with a median age of 60 years, 66.7% being male, and a median BMI of 20.9. All patients had VExUS grade ≥1 on their first venous Doppler exam. All nine patients had a decrease in portal vein pulsatility from initial to final exams. Correlation between portal venous pulsatility and net fluid balance was not statistically significant R= 0.33 (P= 0.39). Other parameters, including VExUS grade, IVC diameter, HV and RV Doppler changes from initial to final ultrasound exams showed variable changes in the post-operative period. Conclusion: Venous congestion Doppler ultrasound assessments appear feasible in immediate postoperative lung transplant patients. A multitude of factors beyond fluid status likely affect waveforms.