Citations

Abstract INTRODUCTION Combining Alzheimer's disease blood biomarkers may improve prediction of amyloid positivity (A+) compared with single biomarkers. METHODS Logistic regression models using plasma phosphorylated tau 217 (p‐tau217), amyloid beta (Aβ) 42, and Aβ40 were developed in cognitively impaired (CI) participants from Mayo Clinic Rochester (MCR) and validated in Alzheimer's Disease Neuroimaging Initiative (ADNI) and Mayo Clinic Florida (MCF) cohorts. Performance was measured by area under the curve (AUC) and Probability of Amyloid Positivity Score (PAPS). RESULTS Plasma p‐tau217 alone showed high AUC (95% confidence intervals) across cohorts MCR, 0.928 (0.900–0.953); ADNI, 0.938 (0.915–0.959); MCF, 0.935 (0.893–0.970). Adding Aβ42 to regression models yielded marginal model improvement MCR, 0.940 (0.915–0.963); ADNI, 0.945 (0.922–0.965); MCF, 0.960 (0.925–0.986). Utilization of two cutpoints (≥ 90% sensitivity and specificity), yielded ≤ 10% intermediate results for p‐tau217, and ≤ 8% for p‐tau217+Aβ42. Addition of Aβ40 did not improve models’ performance. DISCUSSION An immunoassay‐based p‐tau217 PAPS model accurately predicted amyloid positivity across independent CI cohorts and achieved confirmatory‐test performance with two cutpoints. The added value of Aβ42 was modest and cohort dependent, supporting the potential of use of p‐tau217–based PAPS in clinical workflows.

Purpose To describe whether subspecialty training, specifically arthroscopic fellowship training, influences intraoperative range‐of‐motion (ROM) gains, postoperative ROM retention, and lysis of adhesions (LOA) complication rates. Methods Between August 1989 and May 2025, all patients who underwent arthroscopic LOA for stiffness after primary total knee arthroplasty (TKA) at a single multisite academic institution with a minimum follow‐up of 3 months were reviewed. Cases were stratified by the surgeon's training: 1 group with arthroscopic fellowship training and another with nonarthroscopic or no fellowship training. Primary outcomes were intraoperative ROM change and postoperative ROM retention compared with intraoperative and pre‐TKA baseline values. Revision and periprosthetic joint infection rates were also collected. Results A total of 94 LOA cases were identified, where 48 (51.1%) were performed by nonarthroscopically trained surgeons. Intraoperative ROM improvements were similar between groups in both knee flexion (35.2° arthroscopic vs 31.1° nonarthroscopic, P = .130) and extension (2.43° vs 3.91°, P = .079). Compared with the intraoperative ROM, procedures performed by arthroscopically trained surgeons showed significantly better long‐term retention of both flexion (loss of 4.85° vs 15.98°, P = .006) and extension (gain of 0.50° vs loss of 1.58°, P = .036) at postoperative follow‐up. When compared with preprimary TKA baseline ROM, flexion at follow‐up was slightly improved in the arthroscopic group but declined significantly in the nonarthroscopic group (gain of 1.66° vs loss of 21.76°, P < .001). Eight revision TKAs (8.51%) occurred after LOA, 6 of which involved nonarthroscopic surgeons, and 1 periprosthetic joint infection case was reported. Conclusions LOA performed by arthroscopic fellowship‐trained surgeons results in significantly better retention of postoperative ROM than nonfellowship‐trained surgeons when used for arthrofibrosis after TKA. Level of Evidence Level III, retrospective comparative study.

Objective Hospitalization, particularly for surgery, represents a period of heightened stress. We evaluated how frailty attenuates the association of rheumatoid arthritis (RA) with negative health outcomes after elective noncardiac surgery. Methods We conducted a cross‐sectional study using the National Inpatient Sample (2018 to 2020), including adults (aged ≥18 years) with elective hospitalizations with noncardiac surgery. Frailty was measured using the Hospital Frailty Risk Score (HFRS). Surgeries were categorized by risk level. Outcomes included discharge health resources need (DHRN), composite adverse clinical events (CACE), and death. Results Among 8,800,359 hospitalizations (2.14% among patients with RA), 73.36% underwent intermediate‐risk surgery and 62.25% had HFRS above 0. DHRN occurred in 28.9%, CACE occurred in 0.93%, and all‐cause mortality occurred in 0.17%. A 10‐point increase in HFRS was associated with a 3.8‐fold increased DHRN, 8.5‐fold increased CACE, and 22.8‐fold increased mortality. RA was not independently associated with CACE (adjusted odds ratio [aOR] 0.91; 95% confidence interval [CI] 0.82–1.01; P = 0.08) or death (aOR 0.90; 95% CI 0.71–1.15; P = 0.41) but was significantly associated with DHRN (aOR 1.28, 95% CI 1.25–1.31; P < 0.001) after adjusting for confounders and frailty. In sensitivity analysis, RA had 10% higher relative odds of DHRN following orthopedic (aOR 1.10; 95% CI 1.07–1.13; P < 0.001) but not nonorthopedic intermediate‐risk surgery (aOR 1.10; 95% CI 0.98–1.23; P = 0.11). Conclusion RA was associated with higher odds of DHRN after orthopedic intermediate‐risk surgery but not CACE or inpatient mortality. Moreover, HFRS was associated with DHRN, CACE, and death. These findings underscore the need for disease‐specific clinical considerations and highlight the potential utility of HFRS in discharge planning.

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.

Introduction Krackow Type II valgus deformity is defined by attenuation of the medial collateral ligament (MCL). However, little quantitative information exists about associated intra-operative MCL laxity. Furthermore, a corollary may exist in varus deformity with associated lateral ligament laxity but is poorly described. Robotic-assisted total knee arthroplasty (raTKA) includes quantitative assessment of intraoperative ligament function. This study evaluated whether increased preoperative medial or lateral radiographic joint space width (JSW) in valgus or varus knees, was associated with increased intraoperative soft tissue laxity of the respective compartment. Methodology Intraoperative data from 348 consecutive raTKAs with 270 varus knees (hip-knee-ankle angle [HKA]<-2°), and 78 valgus knees, (HKA>2°) were retrospectively reviewed. For varus knees, lateral JSW was measured on preoperative, standing anteroposterior radiographs to determine lateral widening (threshold 8.0mm). For valgus knees, medial JSW was evaluated to determine medial widening (threshold 7.0mm). Intraoperative medial and lateral gaps at 0° and 90° had been recorded during manual stress testing. Linear regression was performed to determine associations between intra-operative gaps, radiographic JSW, and HKA. Results 51 varus knees demonstrated lateral widening and 15 valgus knees had medial widening. In varus knees, lateral JSW was positively associated with the lateral extension (β=0.76, P <0.001) and flexion (β=0.74, P <0.001) gaps. Similarly, for valgus knees, medial JSW was positively associated with the medial extension (β=0.75, P <0.001) and flexion (β=0.77, P <0.001) gaps. Conclusion Increased preoperative radiographic JSW of the medial and lateral compartment in valgus and varus knees, predicted increased intraoperative gaps of that compartment, consistent with ligament attenuation.

Transcranial magnetic stimulation can provide noninvasive measures of cortical excitability and plasticity, but relationships between these measures and clinically observable features of autism are not fully characterized. Nineteen autistic participants aged 15 to 40 years were included in the analysis of a left primary motor cortex continuous theta-burst stimulation (cTBS) biomarker protocol. Motor evoked potentials were measured at baseline and at seven assessments from 5 to 60 min after stimulation. Linear mixed-effects models evaluated whether clinical measures moderated the post-stimulation motor evoked potential log-response ratio over time. Aberrant Behavior Checklist (ABC) and Attenuated Behavior Questionnaire (ABQ) analyses were restricted to the same 15 participants with caregiver-informant assessments. Catatonia severity, social impairment, ABQ Motor Total, ABQ Total, and cognitive ability did not significantly moderate the post-stimulation response. ABC Inappropriate Speech was associated with progressively greater post-stimulation facilitation (standardized Time-by-Inappropriate Speech interaction: beta = +0.688, SE = 0.210, 95% CI +0.276 to +1.099; Holm-adjusted P = .008 across eight informant-rated models). Two individual speech-related items ("Talks excessively" and "Talks to self loudly") survived false-discovery-rate correction. An exploratory eight-item ABC phenotype showed a large descriptive in-sample association (beta = +0.904, SE = 0.200, P less than .001) and directionally positive held-out performance. However, full-pipeline permutation tests were nonsignificant for both Pearson (r = .357, two-sided empirical P = .360) and Spearman correlations (rho = .446, two-sided empirical P = .261). Caregiver-rated inappropriate speech may be associated with altered post-cTBS motor cortical facilitation in autism. The candidate phenotype remains hypothesis-generating and requires independent validation.

Purpose To compare lower extremity soft tissue injury and revision surgery rates for patients with anorexia nervosa (AN) and bulimia nervosa (BN) compared with matched controls. Methods This retrospective cohort study used a deidentified claims database. Patients were included if they carried an International Classification of Diseases code for AN or BN. Respective matched cohorts for AN and BN were created using propensity score matching. Primary and revision surgeries for anterior cruciate ligament (ACL) reconstruction, posterior cruciate ligament reconstruction, knee collateral ligament reconstruction, meniscus repair or meniscectomy, and any ankle ligament reconstruction were identified by their CPT codes. Patients over the age of 40 and without a minimum 2‐year follow‐up after primary surgery were excluded. Differences in prevalence and revision rates were analyzed. Results A total of 56,146 patients with AN and 42,630 patients with BN were included in this study with equal numbers in respective matched cohorts. Patients with BN showed an increased risk of ACL injury (relative risk = 1.32, P = .019), medial collateral ligament injury (1.17, 0.04), calcaneofibular sprain (1.92, <0.001), deltoid sprain (1.41, 0.004), and unspecified ankle sprain (1.44, <0.001). Patients with AN showed an increased risk for calcaneofibular sprain (1.25, 0.007), deltoid sprain (1.28, 0.015), and unspecified ankle sprain (1.17, <0.001). Patients with BN were more likely to have revision ACL repair (1.89, 0.02), partial meniscus revision (3.44, <0.001) and any meniscus revision (4.74, <0.001) while patients with AN were more likely to have an ACL revision (2.81, <0.001), partial meniscus (4.37, <0.001), and any meniscus (4.52, <0.001). Conclusions In this study, patients with AN and BN had a significantly increased risk for various knee and ankle injuries and revision surgeries compared with matched controls. Additionally, patients with AN and BN who sustained these injuries were more likely to undergo a revision surgical procedure within the first 5 years of the primary procedure. Level of Evidence Level III, retrospective comparative study.