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Importance Delirium is a state of acute confusion characterized by deficits in attention that occurs commonly during hospitalization and is associated with adverse outcomes; however, the association of delirium with longitudinal cognitive trajectories is not fully understood. Objective To evaluate the association of delirium during hospitalization with subsequent development of mild cognitive impairment (MCI), dementia, and longitudinal cognitive trajectories. Design, Setting, and Participants This cohort study used data from participants with hospitalizations in the Mayo Clinic Study of Aging (MCSA) from October 2004 to December 2023. The MCSA is a prospective, population-based longitudinal study of cognitive aging among residents of Olmsted County, Minnesota. Of participants enrolled in the MCSA between 2004 and 2023, individuals who experienced 1 or more hospitalization prior to their last MCSA encounter were included in this study. Participants with dementia at MCSA enrollment or prior to first hospitalization were excluded. Follow-up continued until development of MCI or dementia, last MCSA visit, or the end of the study. Exposure Delirium was identified using a validated natural language processing algorithm applied to clinical notes from hospitalizations, associated emergency department visits, and follow-up within 30 days after hospitalization. Delirium status was modeled as a time-dependent exposure. Main Outcomes and Measures Incident MCI and dementia were assigned through MCSA expert consensus evaluations, including neuropsychological testing performed every 15 months. Association between delirium and development of MCI or dementia was assessed using Cox proportional hazards regression, adjusted for patient age, sex, level of education, and apolipoprotein E (APOE) ε4 allele carrier status; cognitive trajectories were assessed with linear mixed-effects models. Results Of 7030 participants enrolled in the MCSA, 3542 individuals experienced 1 or more hospitalization prior to their last MCSA encounter and were included, and 41 participants with dementia at enrollment or prior to first hospitalization were excluded. The cohort included 3501 participants with at least 1 hospitalization. Median (IQR) age was 74.1 (66.6-80.9) years, 1676 participants (47.9%) were female, median (IQR) level of education was 14 (12-16) years, and 910 participants (26.0%) were APOE ε4 carriers. During a median (IQR) follow-up of 7.2 (4.1-10.4) years, 75 participants (2.1%) had delirium documented within 30 days of hospitalization. Delirium was associated with increased risk of MCI (adjusted hazard ratio [aHR], 3.67; 95% CI, 2.19-6.15) and dementia (aHR, 5.39; 95% CI, 2.94-9.85) and with accelerated decline in longitudinal cognitive testing. Conclusions and Relevance In this cohort study among adults in the MCSA, including those with unimpaired cognition at baseline, delirium during hospitalization was strongly associated with increased risk of MCI and dementia and accelerated cognitive decline in subsequent years.

Objective During open chondral defect preparation, audible debridement sound changes mark the transition from deep cartilage to the calcified cartilage layer. We developed a novel curette microphone to characterize these audio feature differences during arthroscopic defect preparation. Design A piezoelectric curette microphone was used to transmit and record debridement sound from 12 defect preparations (6 deep cartilage, 6 CCL) using human osteochondral allograft remnants. Live audio from the device was used to stop each debridement at the intended level, which was verified histologically. Spectrograms and power-spectral density plots were used to describe the audible transition from deep cartilage to CCL. We compared 22 audio features describing loudness, frequency, and complexity between the two tissue levels. Results Curette strokes against the deep cartilage were louder, higher frequency, and more acoustically complex than strokes against the CCL (p < 0.001). Cartilage debridement generated acoustically complex frequency bands above 2.5 kHz that diminished upon reaching the CCL. Debridement of the CCL produced a simpler audio profile that was predominant below 350 Hz. Conclusion The novel curette microphone presented here transmits high-fidelity debridement audio that can be used to accurately distinguish tissue depth based on the distinct audio profiles of the deep cartilage and CCL.

ABSTRACT Background and Objectives Among patient with early‐stage breast cancer, breast conservation surgery (BCS) is the most performed surgery, utilized in approximately two‐thirds of patients. While 5‐year overall‐survival rates are strong—typically above 90%—additional re‐excisions can occur in up to 25% of patients who undergo index BCS and some patients will require subsequent surgery for new breast cancer or recurrences. As such, these additional procedures can complicate patients’ pathway to survivorship, negatively impact quality of life, and lead to excess healthcare costs. Methods This retrospective cohort study used linked claims and an electronic healthcare record database to (1) characterize patients at higher risk for additional breast oncologic surgery (aBOS) following BCS, and (2) quantify the long‐term financial impact of aBOS after BCS. In total, 87,190 patients with breast cancer, who had an index BCS between January 1, 2012, to March 31, 2023, were followed for up to 5‐years post‐operatively. Patients with and without aBOS were analyzed, comparing demographics, tumor characteristics, healthcare utilization, and per‐person‐per‐month (PPPM) costs. Results Twenty‐three percent ( n = 20,212) of patients underwent aBOS. These patients were younger, had higher tumor grades and larger tumor sizes, and incurred greater healthcare costs compared to patients who did not undergo a secondary surgery. Conclusion This study highlights significant factors influencing BCS outcomes and healthcare utilization, underscoring the need for tailored therapeutic strategies for patients with breast cancer.

BACKGROUND: Type 2 long-QT syndrome results from KCNH2 -encoded Kv11.1 loss-of-function, but whether secondary inward-current dysfunction amplifies dysfunction remains unclear. METHODS: We characterized sodium ( SCN5A , I Na ) and L-type calcium channel ( CACNA1C , I Ca ) function in KCNH2-G604S and variant-corrected isogenic control induced pluripotent stem cell–derived cardiomyocytes (iPSC-CMs). Whole-cell patch-clamp measured action potential duration at 90% repolarization (APD90), and potassium (I Kr ), sodium (I Na ), and calcium (I Ca, L ) currents. Fluo-4 imaging quantified calcium transients. A modified Kernik-Clancy iPSC-CM model incorporated experimentally measured persistent I Na,L and I Ca,L fractions and simulated isolated and combined current defects. RESULTS: KCNH2-G604S caused severe I Kr loss-of-function (72.5% reduction). APD90 was prolonged in G604S-iPSC-CMs (765±58 ms) compared with isogenic controls (368±37 ms; P <0.005), with early afterdepolarizations in 50% of G604S cells. Nifedipine, verapamil, and mexiletine successfully shortened APD90 and abolished early afterdepolarizations. Compared with isogenic control, I Na,L (0.60±0.1% versus 0.26±0.06%; P <0.01), persistent I Ca,L (2.88±0.55% versus 1.26±0.35%; P <0.05), and calcium transient decay times ( P <0.0001) were greater in G604S iPSC-CMs. Increased persistent I Ca,L was phenocopied by E-4031 in isogenic controls and reduced by nifedipine in G604S iPSC-CMs. In silico modeling revealed that the I Kr defect alone prolonged APD90 to only 620 ms. The addition of the observed I Na,L defect had a small additive effect (+20 ms); however, incorporating persistent I Ca,L synergistically extended APD90 to 758 ms, replicating the experimental phenotype. Flux dynamics analysis indicated that this persistent Ca 2+ entry suppresses the forward-mode sodium-calcium exchanger, forcing a compensatory reliance on sarcoplasmic-endoplasmic reticulum Ca-ATPase that primes for calcium instability. CONCLUSIONS: The KCNH2-G604S variant drives a severe multihit phenotype via primary I Kr loss-of-function and secondary state-dependent gain-of-function in persistent I Ca,L . These comprehensive validations demonstrate that the remodeled persistent I Ca,L acts as the essential amplifier driving extreme action potential duration prolongation and Ca 2+ mishandling.

Abstract Objective. X-ray angiography and fluoroscopy systems are used to diagnose and treat congenital heart disease in pediatric patients. Among the substantial variabilities in this clinical patient population is that patient weight ranges from <1 kg premature infants to large adolescents. The primary aim of this work was to assess whether an air gap or antiscatter grid is more efficient to mitigate the detrimental influence of scatter radiation on pediatric image quality. Approach. The experimental approach was guided by a 2 year review of pediatric patient imaging conditions. Uniform density water-equivalent phantoms with thickness in the range 6–24 cm were used. For each phantom thickness, the x-ray technique was manually set to mimic the technique selected by automatic dose rate control. The influence of four combinations of air gap and ratio 15:1 antiscatter grid on test object SNR was measured. The air gap was varied by changing the x-ray source to detector distance from 107 to 120 cm. The analytical methods estimated pixel-specific snr 2 contributions to object SNR 2 , thus providing for the use of iodine disks and pediatric implantable devices as test objects. Main results. Patient weight ranged from 0.5 to 134 kg. The relationship between patient water equivalent thickness and weight was demonstrated. For all phantom thicknesses, object SNR was highest using a long air gap, non-grid technique. Decreasing the air gap between the phantom and detector and use of the anti-scatter grid both degraded SNR. These major findings were consistent between iodine disks and clinical devices as test objects. Significance. The findings of this phantom study suggest that a long air gap, non-grid imaging technique may improve radiation dose efficiency of fluoroscopy and angiography imaging across a broad range of pediatric patient sizes.

Abstract INTRODUCTION Plasma phosphorylated tau 217 (p‑tau217) immunoassays are increasingly being used to assess Alzheimer's disease (AD) pathology despite limited data affirming test reliability over time. METHODS Clinical performance of the Fujirebio Lumipulse G p‑tau217 assay was assessed in 744 Mayo Clinic patients presenting for evaluation of cognitive impairment between July 2024 and December 2025. Cerebrospinal fluid p‑tau181/amyloid beta 42 or amyloid positron emission tomography, within 1 year of p‐tau217 testing, were used as reference. Analytical robustness was evaluated by tracking result frequencies over time, conducting quality control checks, performing 10 lot‑to‑lot comparisons, and comparing two versions of reagents. RESULTS Diagnostic accuracy for detection of AD pathology was 93% (95% confidence interval 91–95) with 23% intermediate results. Reduced estimated glomerular filtration rate was associated with increased intermediate results among amyloid‐negative individuals. Result frequencies remained stable, average imprecision was 8%, and analytical bias between lots and version changes were ≤ 11%. DISCUSSION The findings support plasma p‐tau217 reliability in clinical practice for evaluation of cognitively impaired individuals.

Purpose To identify risk factors for medial meniscus posterior root tears (MMPRT) and arthroplasty‐free survival in postmenopausal women, while secondary objectives included analyzing menopause‐specific factors associated with MMPRT and defining risk factors for conversion to arthroplasty in patients with a confirmed MMPRT. Methods All patients at our institution with a diagnosed meniscal tear through December 2024 were identified. From this cohort, women with a menopausal diagnosis preceding their meniscal tear were matched one‐to‐one with men by age and body mass index. Imaging studies were reviewed to identify MMPRTs. Subsequent arthroplasty, Charlson Comorbidity Index, menopausal type (surgical or physiologic), hormone replacement therapy, bisphosphonate usage, and bone mineral density were recorded. Logistic and Cox regression were used to define risk factors for MMPRT and arthroplasty; survivorship was determined using Kaplan‐Meier analyses. Results The final cohort consisted of 1564 patients (n = 782 women) with a median age of 63 years, of which 244 patients (15.6%) had MMPRT. Age and female sex were associated with MMPRT. The presence of an MMPRT, female sex, body mass index, and Charlson Comorbidity Index were associated with arthroplasty. Among postmenopausal women, age at menopause, surgical menopause, hormone replacement therapy, and bone mineral density were associated with MMPRT. For patients with MMPRT, female sex was associated with arthroplasty. Ten‐year survivorship‐free from arthroplasty in patients with MMPRT was 53.5% for women and 78.4% for men ( P = .02). Conclusions Postmenopausal status, age, and hormone replacement therapy usage are risk factors for MMPRT. Compared with men, postmenopausal women with MMPRT exhibit reduced arthroplasty‐free survival, underscoring the need for targeted interventions. Level of Evidence Level III, retrospective comparative study.

Abstract Skin and soft tissues infections (SSTIs) are common conditions, affecting millions worldwide. SSTIs range from uncomplicated cellulitis to necrotizing fasciitis and can be divided into non-purulent and purulent forms. Non-purulent SSTI is most commonly associated with beta-haemolytic streptococci, while purulent SSTI is typically associated with Staphylococcus aureus . Cellulitis most commonly presents with acute warmth, pain, tenderness to palpation, erythema, and oedema. Skin abscess typically presents with a fluctuant tender area with erythema. Laboratory testing is of limited use in most patients. Point-of-care ultrasound is useful for distinguishing cellulitis from abscess if the diagnosis is unclear. Management of SSTI includes antibiotics such as penicillin VK, dicloxacillin, or a cephalosporin, while treatment for skin abscess includes incision and drainage, with antibiotics recommended in select patients. Patients should elevate the affected extremity when possible, and non-steroidal anti-inflammatory drugs may reduce pain and inflammation. The effectiveness of decolonization for patients with recurrent cellulitis or skin abscess is controversial. While most patients with cellulitis or skin abscess are appropriate for discharge with follow-up, patients with sepsis and those with challenges adhering to therapy, immunosuppression, or failed outpatient therapy should be referred to the emergency department. Novel antibiotics such as tedizolid, delafloxacin, omadacycline, and ceftaroline may be considered in select cases.