Citations

Abstract Purpose Failed stapes surgery presents a diagnostic challenge requiring high-resolution imaging to guide revision. Energy-integrating detector CT (EID-CT) is widely used but limited by spatial resolution and metal artifact. Photon-counting CT (PCCT) offers improved spatial resolution and reduced noise, with potential advantages in temporal bone imaging. The purpose of this study was to compare PCCT and EID-CT in identifying etiologies of failed primary stapes surgery, with emphasis on diagnostic accuracy, interobserver agreement, and interpreter confidence Methods In this retrospective study, 38 patients with failed primary stapes surgery who underwent successful revision surgery and pre-revision CT were included; 18 underwent PCCT and 20 underwent EID-CT. Three expert reviewers independently determined the cause of surgical failure, compared against the reference standard of intraoperative findings at revision. Diagnostic accuracy, interobserver agreement (Fleiss kappa), and reader confidence were compared between modalities. Results Overall interobserver agreement was substantially higher with PCCT (κ = 0.75; 95% CI, 0.60–0.90) than EID-CT (κ = 0.44; 95% CI, 0.30–0.59), with improved agreement observed across etiologies of failure; confidence intervals were non-overlapping for overall agreement and ossicular discontinuity. Consensus diagnostic accuracy was comparable between modalities (88.9% PCCT vs 85% EID-CT; p = 1.00), as was interpreter confidence (4.33 PCCT vs 4.17 EID-CT; p = 0.29). Conclusion In this small cohort, PCCT and EID-CT demonstrated similar diagnostic accuracy and reader confidence, whereas PCCT demonstrated significantly higher interobserver agreement, suggesting more reproducible assessment of failed stapes surgery and a potential role in supporting revision surgical planning.

Purpose To evaluate the association between myocardial infarction (MI) timing within 2 years prior to arthroscopic rotator cuff repair (aRCR) and postoperative cardiac, medical, and surgical complications. Methods The PearlDiver Mariner Database (2010‐2022) was queried to identify patients undergoing aRCR (CPT‐29827). Patients with an MI within 2 years before surgery were propensity matched 1:4 to controls without MI based on demographics and comorbidities. Subgroup analyses evaluated MI timing (0‐6, 6‐12, 12‐18, and 18‐24 months), MI type (type 1 vs type 2, ST‐elevation MI vs non‐ST‐elevation MI), percutaneous coronary intervention (PCI) status, guideline‐directed medical therapy, and infarct location. Primary outcomes included 90‐day medical and 2‐year surgical complications. Odds ratios with 95% confidence intervals were calculated. Results A total of 2886 patients with prior MI were matched to 10,613 controls. Prior MI increased the odds of postoperative MI (odds ratio, 3.48; 95% confidence interval, 2.13, 8.32). The highest risk of postoperative MI occurred when aRCR was performed within 6 months of MI (odds ratio, 7.55; 95% confidence interval, 4.38, 13.01), with no significant elevation beyond this window. Type 1 MI was associated with postoperative MI and mortality, whereas type 2 MI was associated with acute kidney injury, pneumonia, and readmission. Both ST‐elevation MI and non‐ST‐elevation MI were linked to increased postoperative MI risk. Patients without PCI showed broader postoperative complications, including mortality, acute kidney injury, and stiffness, compared with those who underwent PCI. Conclusions Recent MI is associated with increased postoperative risk of MI after aRCR, particularly when surgery is performed within 6 months. Patients without PCI experience additional vulnerability. Level of Evidence Level III, retrospective comparative study.

Abstract Objective Low back pain (LBP) is a leading cause of pain and disability worldwide. Recent studies demonstrate a vertebrogenic model involving the basivertebral nerve (BVN) as a cause of chronic LBP. Vertebral endplates are highly innervated by the BVN, and literature shows type 1 and 2 Modic changes at vertebral endplates are a source of vertebrogenic low back pain (VBP). As a result, intraosseous radiofrequency ablation of the BVN is a minimally invasive outpatient procedure used to treat VBP. We conducted a retrospective review of 1,145 patients that have undergone BVN ablation to assess for safety and complication management. Methods Chart reviews were conducted to obtain demographic and pre-procedural information regarding patient gender, age at the time of BVN ablation, duration of LBP, and BMI. Post-procedure information derived from chart notes included vertebral levels ablated and post-BVN ablation complications, which were categorized as increased LBP > 7 days, increased radicular pain > 7 days, lower extremity weakness, infection, vertebral compression fracture, superficial bleeding, spinal or epidural hematoma, serious neurological injury, visit to the ER, and deep vein thrombosis/clot. Results 1,145 patient charts were reviewed showing an overall complication rate of 3.2% (37 complications). Increased radicular pain was the most common complication at 2.2% (25 complications) and resolved completely in all but one patient. The overall complication rate fell to 1.1% (13 complications) when the 24 cases of transient radicular pain were not counted as adverse events. Conclusions In this multicenter retrospective review, the overall rate of complications related to BVN ablation was low (3.2%). The most common complication was temporary radicular pain that resolved with conservative care. These findings suggest that BVN ablation is a safe treatment for VBP in real-world clinical settings.

Abstract The development of biocompatible and biologically responsive scaffolds remains a key challenge for bone tissue engineering. Here, we report an enzyme-degradable, metal-free click-cross-linked organic–inorganic nanohybrid (Enz-Deg-Click-ON) scaffold with high biocompatibility for bone repair. The formulation was synthesized using a cyclooctyne-functionalized poly(propylene fumarate) polyphosphoester (PPF-poly(PE-BCN)) and azide-terminated dendritic polycaprolactone (PCL) with a polyhedral oligomeric silsesquioxane core (POSS-PCL-N3) via strain-promoted alkyne-azide cycloaddition (SPAAC) bioorthogonal click chemistry. The incorporation of phosphate-containing linkages enabled alkaline phosphatase (ALP)-responsive degradation. The scaffold exhibited rapid catalyst-free crosslinking, tunable swelling, and suitable mechanical properties. In vitro studies demonstrated excellent cytocompatibility, robust stem cell proliferation, and enhanced osteogenic differentiation with an elevated level of ALP and Runx2 expression. Enzyme-triggered degradation was confirmed in the presence of ALP. In the in vivo rat calvarial defect model, the scaffold significantly improved bone regeneration, as shown by an increased bone volume, mineral density, and defect coverage. Histological and immunofluorescence analyses revealed enhanced collagen deposition, angiogenesis, and osteogenesis. These results indicate that the Enz-Deg-Click-ON system provides a dynamic, bioresponsive platform for bone repair.

ABSTRACT Background Mobility functional status is inconsistently recorded in electronic health records. Recent advances in Large Language Models (LLMs) enable automated extraction of functional information from unstructured clinical notes. Leveraging a validated functional LLM with high performance in mobility extraction, we aimed to study the association between LLM‐derived mobility functional status and clinical outcomes, including emergency department (ED) visits, hospitalizations, and mortality. Methods Individuals aged 60 years and older enrolled in the Mayo Clinic Study of Aging, with documented clinical notes in 2022 were included. Individuals without any identifiable functional information were excluded. The LLM‐derived mobility functional status categorized mobility as impaired or unimpaired, across the five mobility domains as classified by International Classification of Functioning, Disability, and Health. Clinical outcomes in 2023 were extracted from the Rochester Epidemiology Project database. Logistic regression models assessed associations between mobility impairment and outcomes, adjusted for age, sex, Elixhauser comorbidity index, and education. Results Three thousand three hundred thirty‐seven individuals were screened, of whom three hundred forty‐three had no functional information. Two thousand nine hundred ninety‐four individuals were analyzed. 79.4% had at least one mobility impairment. Higher mobility impairment is associated with older age and greater Elixhauser comorbidity. Individuals with 3 or more impairments had an increased adjusted odds of ED visits (Adjusted Odds Ratio (aOR): 2.18 (1.64, 2.90)) and hospitalizations (aOR: 2.35 (1.51, 3.65)) compared to unimpaired individuals ( p < 0.001), while mortality did not demonstrate a significant association with mobility impairment. Conclusion LLM‐derived mobility functional status assessment was associated with ED visits and hospitalization, but not with all‐cause mortality after adjustment. Prospective validation and evaluation of incremental discrimination, calibration, and clinical utility are needed before clinical implementation.

Abstract Orthoebolaviruses, including Ebola virus (EBOV) and Bundibugyo virus (BDBV), cause sporadic outbreaks and devastating hemorrhagic infections in humans. A significant challenge that impedes the study of filoviruses is that the infectious virus can only be handled in biosafety level 4 (BSL4) facilities due to their extreme virulence. Life cycle modeling systems that use minigenomes and transcription/replication-competent virus-like particles (trVLPs) are powerful tools for studying these virus’ biology and to explore antiviral therapies under BSL2 conditions. To date, these powerful tools have only been utilized in vitro in cell culture systems. In this work, we demonstrate the use of EBOV trVLPs in vivo. We report the fine specificity of first infection events in a model of EBOV injection in the skin. Cre recombinase expressing monocistronic EBOV trVLPs were packaged and used to inject Cre reporter mice intradermally (ID). Initial infection events were monitored in living animals by luciferase imaging and then by flow cytometry to track cell-specific expression of Cre-activated GFP. By this approach, EBOV trVLPs were shown to directly infect T cells, monocytes, dendritic cells (DCs) with notably high first infections of skin-resident Langerhans cells (LCs) in the skin barrier and its draining lymph node. EBOV trVLPs were next tested as an in vivo tool to assess antiviral therapies by testing the ability of an EBOV vaccine to reduce trVLP luciferase levels after infection in the skin. This work demonstrates first in vivo use of EBOV trVLPs and provides proof of concept for their use as an in vivo BSL2 model to more rapidly develop antiviral agents and vaccines.

Background Neurofibromatosis type 1 (NF1) is a genetic disorder in which plexiform neurofibromas (PNs) develop in approximately 30% to 50% of affected individuals, often causing substantial morbidity. Treatment of NF1-associated PNs is challenging due to disease variability and tumor complexity. Observations In the Phase 2b ReNeu trial (NCT03962543), mirdametinib, a mitogen-activated protein kinase kinase 1/2 (MEK) inhibitor, demonstrated efficacy and a manageable safety profile in children and adults with symptomatic PNs, achieving confirmed objective responses in 52% of children and 41% of adults, with substantial reductions in target tumor PN volume and improvements in patient- and parent proxy-reported outcomes. However, dermatologic adverse events (AEs) are common with MEK inhibitors, including mirdametinib, and can impact adherence and quality of life. While the ReNeu protocol included supportive care considerations for skin reactions associated with mirdametinib, some investigators recognized a need for more detailed guidance. The ReNeu Scientific Steering Committee, in collaboration with oncology and oncodermatology experts, developed expert-driven recommendations for the proactive management of mirdametinib-related skin AEs. Conclusions These strategies emphasize early recognition, individualized care, and timely intervention to help reduce the severity of mirdametinib-related skin AEs, minimize dose modifications, and support treatment continuity and long-term treatment goals. Although these recommendations were specifically developed for mirdametinib based on ReNeu trial experience, they may also provide practical guidance for managing skin AEs associated with other MEK inhibitors in clinical practice.

Summary: Bone defects are among the most challenging problems treated by limb reconstruction surgeons and orthopaedic traumatologists. Bone transport is a biological reconstruction technique which harnesses distraction osteogenesis to create new bone in critical bone defect. This technique has been successfully performed with a variety of internal and external solutions. This work introduces a newly available technology which provides a fully implantable, all-internal solution (eg, without the need for external fixation) for bone transport with the option to simultaneously address residual limb length discrepancy.