Citations

Abstract Single‐molecule immunoassay is a reliable technique for the detection and quantification of low‐abundance blood biomarkers, which are essential for early disease diagnosis and biomedical research. However, current single‐molecule methods predominantly rely on endpoint detection and necessitate signal amplification via labeling, which brings a variety of unwanted effects, like matrix effect and autofluorescence interference. This study introduces a real‐time mass imaging‐based label‐free single‐molecule immunoassay (LFSMiA). Featuring plasmonic scattering microscopy‐based mass imaging, a 2‐step sandwich assay format enables background reduction, minimization of matrix effect by dynamic tracking of single binding events, and fully leveraging real‐time data for improved measurement precision through a Bayesian Gaussian process model, the LFSMiA enables ultra‐sensitive and direct protein detection at the single‐molecule level in neat blood sample matrices. LFSMiA measurement is demonstrated for interleukin‐6 and prostate‐specific antigen in buffer, undiluted serum, and whole blood with sub‐femtomolar detection limits and eight logs of dynamic ranges. Moreover, comparable performance is achieved with an inexpensive miniaturized setup. To show its translational potential to clinical settings and point‐of‐care diagnostics, N‐terminal pro‐B‐type natriuretic peptide is examined in patient whole blood samples using the LFSMiA and results in a strong linear correlation (r > 0.99) with standard clinical lab results.

Purpose To establish international expert consensus on surgical techniques, complications, and rehabilitation protocols for lateral extra‐articular procedures (LEAPs) performed adjunctively with anterior cruciate ligament reconstruction. Methods Fifty‐five knee surgeons from 17 countries on 5 continents completed a 3‐round modified Delphi process. In the final round, 16 statements on LEAP techniques and complications were scored on a 5‐point Likert scale; ≥75% “agree/strongly agree” constituted consensus. When appropriate, strength of recommendation was graded. Statements lacking support were revised until consensus or abandonment. Results Six statements achieved unanimous consensus (100%), 2 had strong consensus (90%‐99.9%), and 3 reached consensus (75%‐89.9%); 4 were removed. Key technical recommendations were as follows: (1) in iliotibial band procedures, the graft strip should pass beneath the lateral collateral ligament; (2) an anatomic technique is mandatory for anterolateral ligament reconstruction; and (3) no single LEAP is clinically superior to another. Unanimous agreement indicated that modern LEAPs do not increase lateral compartment osteoarthritis risk, carry a low complication rate, and do not necessitate changes to rehabilitation or return‐to‐play timelines. Conclusions Consensus defined core surgical principles and confirmed the safety of adding LEAPs to anterior cruciate ligament reconstruction. When an iliotibial band graft is used, it should be routed deep to the lateral collateral ligament and fixed between 0° and 60° of knee flexion under low tension. For anterolateral ligament reconstruction, femoral fixation should be in full extension at a posterior‐proximal point relative to the lateral epicondyle. Although no single LEAP proved superiority, adherence to these principles permits safe, effective surgery without altering standard rehabilitation or return‐to‐sport protocols and without increasing osteoarthritis risk. Level of Evidence Level V, expert opinion.

Purpose To define expert consensus on whether and how lateral extra‐articular procedures (LEAPs) should accompany anterior cruciate ligament (ACL) reconstruction to optimize outcomes in ACL‐deficient knees. Methods Fifty‐five knee surgeons from 17 countries on 5 continents completed a 3‐round modified Delphi process. Twenty‐one statements on patient selection for combined ACL reconstruction (ACLR) + LEAPs were graded on 5‐point Likert scales; ≥75% “agree/strongly agree” signified consensus. Strength of recommendation was ranked, and statements failing the threshold were revised or discarded after discussion. Results One statement achieved unanimous agreement (100%): it is strongly recommended to add a LEAP for active patients ≤25 years receiving hamstring‐autograft ACLR to reduce graft failure. Strong consensus (≥90%) supported LEAPs in primary ACLR when grade 3 pivot shift (97.9%), knee hyperextension (97.9%), skeletally immature status (79.5%), revision ACLR (91.5%), return to pivoting sports (93.2%), active patients ≤25 years using nonhamstring grafts (90.7%), grade 3 Lachman test (90%), and when multiple relative risk factors coexist (statement 36, 97.1%). Consensus (75%‐89.9%) favored LEAPs for chronic symptomatic ACL deficiency (86.1%), posterior tibial slope >12° (85.7%), and a history of contralateral ACL injury (88.9%). Eight statements did not reach consensus regarding small‐diameter autografts, female athletes, imaging signs of anterolateral injury (e.g., Segond fracture, lateral femoral‐notch sign), and concomitant meniscal procedures. One statement on LEAPs with primary ACL repair was withdrawn because the project focused on reconstruction. Conclusions International experts strongly recommend adding a LEAP in young active patients undergoing hamstring‐autograft ACLR and in cases of high‐grade rotational or anterior laxity, knee hyperextension, revision surgery, or returning to pivoting sports. Unresolved issues include small graft size, female athletes, imaging findings of rotational instability, and concurrent meniscal procedures, highlighting priorities for future research. Level of Evidence Level V, expert opinion.

ABSTRACT Objective Despite high stand‐alone performance, studies demonstrate that artificial intelligence (AI)‐supported endoscopic diagnostics often fall short in clinical applications due to human‐AI interaction factors. This video‐based trial on Barrett's esophagus aimed to investigate how examiner behavior, their levels of confidence, and system usability influence the diagnostic outcomes of AI‐assisted endoscopy. Methods The present analysis employed data from a multicenter randomized controlled tandem video trial involving 22 endoscopists with varying degrees of expertise. Participants were tasked with evaluating a set of 96 endoscopic videos of Barrett's esophagus in two distinct rounds, with and without AI assistance. Diagnostic confidence levels were recorded, and decision changes were categorized according to the AI prediction. Additional surveys assessed user experience and system usability ratings. Results AI assistance significantly increased examiner confidence levels ( p < 0.001) and accuracy. Withdrawing AI assistance decreased confidence ( p < 0.001), but not accuracy. Experts consistently reported higher confidence than non‐experts ( p < 0.001), regardless of performance. Despite improved confidence, correct AI guidance was disregarded in 16% of all cases, and 9% of initially correct diagnoses were changed to incorrect ones. Overreliance on AI, algorithm aversion, and uncertainty in AI predictions were identified as key factors influencing outcomes. The System Usability Scale questionnaire scores indicated good to excellent usability, with non‐experts scoring 73.5 and experts 85.6. Conclusions Our findings highlight the pivotal function of examiner behavior in AI‐assisted endoscopy. To fully realize the benefits of AI, implementing explainable AI, improving user interfaces, and providing targeted training are essential. Addressing these factors could enhance diagnostic accuracy and confidence in clinical practice.

Abstract Purpose: Adolescents with chronic orthostatic intolerance (COI) experience symptoms related to impaired tolerance of upright posture. Postural Orthostatic Tachycardia Syndrome (POTS) is a specific type of COI, marked by an excessive increase in heart rate (≥40 bpm or an absolute HR >120 bpm) when standing. This study compares Functional Disability Inventory (FDI) scores between adolescents with COI with and without excessive postural tachycardia (POTS subtype). Methods: Patients ≤19 years referred to our POTS program (Aug 2024–Mar 2025) with orthostatic symptoms for>3 months were included. Based on active stand HR, patients were categorized as POTS (HR ≥40 bpm) or COI without excessive postural tachycardia (HR <40 bpm). FDI scores were collected. Chi-square tests assessed group differences. A two-sample t-test compared FDI severity. Linear regression evaluated the association between HR change and FDI score. Results: All data were normally distributed, allowing the use of parametric analyses. Of the 92 patients (46 per group), 78% were female. The mean age was 16.0 ± 1.48 years in the COI group and 16.3 ± 1.7 years in the POTS group, with no significant sex differences between groups. The COI group had a higher mean FDI score than the POTS group, but this difference was not statistically significant. The distribution of FDI severity (mild, moderate, severe) was similar between groups. Linear regression showed a non-significant trend of a 1 bpm increase in heart rate associated with a 0.1055-point decrease in FDI score Conclusion: Functional disability was similar between the COI and POTS groups.

Background: Patient-level value analysis (PLVA) has been applied to several orthopaedic procedures but has not yet been utilized to assess the value of total knee arthroplasty (TKA). The purpose of this study was to evaluate the 1-year episode of care for TKA with use of PLVA to identify characteristics that influence value at both the patient and surgeon level. Methods: The institutional patient-reported outcome (PRO) database was queried for all patients who underwent TKA from 2020 to 2022. Patients were excluded on the basis of an index revision procedure, a pathology other than primary osteoarthritis, unicompartmental knee arthroplasty, robotic-assisted TKA, incomplete baseline or 1-year PROs, concomitant procedures (i.e., bilateral TKA or hardware removal), complications requiring readmission or reoperation, TKA without patellar resurfacing, the use of constrained implants, incomplete cost information, or other hip or knee arthroplasty procedure during the 1-year episode of care. PROs of interest included preoperative and 1-year postoperative Knee injury and Osteoarthritis Outcome Score-Joint Replacement (KOOS-JR) scores. Episode-of-care costs were calculated using time-driven activity-based costing. The 1-year value quotient (V KOOS ) was calculated for each patient as the ratio of the 1-year change in KOOS-JR score to the total episode-of-care cost. Results: A total of 684 patients (62% female; mean age, 68 ± 8 years) met the inclusion criteria. The mean KOOS-JR score significantly increased from baseline (53 ± 11) to 1 year (79 ± 14; p < 0.001), with a mean improvement of 26 ± 16. The mean total episode-of-care cost was $9,563 ± $2,370. There was no significant correlation between episode-of-care costs and the change in KOOS-JR score (r = 0.02; p = 0.581). Surgery performed at an ambulatory surgery center (p < 0.001) and as an outpatient procedure (p = 0.036) were predictive of lower costs. Patient-specific instrumentation (p < 0.001) and a tibial stem extension (p < 0.001) were predictive of higher costs. Older age (p = 0.023) and male sex (p = 0.007) were predictive of less improvement in KOOS-JR scores from baseline to 1 year. Conclusions: Our study identified patient and surgical characteristics that drive costs and PROs in TKA. PLVA can be used to identify “bright spots” in orthopaedic procedures to optimize care delivery. Level of Evidence: Prognostic Level IV . See Instructions for Authors for a complete description of levels of evidence.