A blood-based multi-pathway biomarker assay for early detection and staging of Alzheimer's disease across ethnic groups.

INTRODUCTION: Existing blood-based biomarkers for Alzheimer's disease (AD) mainly focus on its pathological features. However, studies on blood-based biomarkers associated with other biological processes for a comprehensive evaluation of AD status are limited. METHODS: We developed a blood-based, multiplex biomarker assay for AD that measures the levels of 21 proteins involved in multiple biological pathways. We evaluated the assay's performance for classifying AD and indicating AD-related endophenotypes in three independent cohorts from Chinese or European-descent populations. RESULTS: The 21-protein assay accurately classified AD (area under the receiver operating characteristic curve [AUC] = 0.9407 to 0.9867) and mild cognitive impairment (MCI; AUC = 0.8434 to 0.8945) while also indicating brain amyloid pathology. Moreover, the assay simultaneously evaluated the changes of five biological processes in individuals and revealed the ethnic-specific dysregulations of biological processes upon AD progression. DISCUSSION: This study demonstrated the utility of a blood-based, multi-pathway biomarker assay for early screening and staging of AD, providing insights for patient stratification and precision medicine. HIGHLIGHTS: The authors developed a blood-based biomarker assay for Alzheimer's disease. The 21-protein assay classifies AD/MCI and indicates brain amyloid pathology. The 21-protein assay can simultaneously assess activities of five biological processes. Ethnic-specific dysregulations of biological processes in AD were revealed.

A Retrospective Study Characterizing the Radiographic Progression of Hallux Valgus.

BACKGROUND: Hallux valgus deformity is the lateral deviation of the metatarsophalangeal (MTP) joint and is the most common pathology of the great toe, affecting 2%-4% of the population. It is commonly believed that the condition progresses over time both in the magnitude of deformity and development of arthritic changes. To our knowledge, there are rare studies describing the rate of deformity progression and the development of arthritic changes. Our aim is to quantify the progression of hallux valgus and associated arthritic changes in an adult population using radiographs. METHODS: Patients who are 18 years of age and older (mean age: 61.7 years and range: 18.6-94.2) who presented to our institutions between January 1, 2004, and December 1, 2019, were included. Patients were included in the study if they had hallux valgus on weight-bearing radiographs and two such radiographs at least six months apart. Hallux valgus angle (HVA), intermetatarsal angle (IMA), metatarsophalangeal (MTP) arthritis, tarsometatarsal (TMT) osteoarthritis, Hardy-Clapham sesamoid position, and round sign were collected per patient in the initial and final radiographs. Included cases were first studied together in a whole group. Then, cases were separated into three groups based on the time between initial and final radiographs. RESULTS: A total of 52 radiographic records for 43 patients were included. HVA and IMA progress with time; however, progression does not follow a direct relationship with the time elapsed between initial and final radiographs (p = 0.92 and p = 0.35, respectively). The progression of TMT osteoarthritis, sesamoid position, and round sign do not show a dependence on the time elapsed (p = 0.20, p = 0.11, and p = 0.42, respectively). An increase of one sesamoid unit position over baseline is associated with a 0.85-degree increase in IMA. A one-unit progression of sesamoid position at baseline raises the odds of MTP osteoarthritis progression at the follow-up visit by 2.14 (OR = 2.14, p = 0.0007, CI = [1.35, 3.83]). A HVA increase of one degree increases the odds of TMT osteoarthritis progression at follow-up by a factor of 1.17 (OR = 1.17, p = 0.0005, CI = [1.07, 1.34]). Patients with MTP arthritis at the initial visit have 3.77 times higher odds of round sign progression on their follow-up visit (OR = 3.77, p = 0.027, CI = [1.16, 13.13]). DISCUSSION: Hallux valgus progression can be quantified. Upon their first visit, a patient's hallux valgus parameters can be utilized to demonstrate expected progression. Progression of the deformity and arthritic changes is slow. Nonetheless, the results should be considered by surgeons and patients when developing a treatment plan with patients.

Multi-segment foot kinematics during gait following ankle arthroplasty.

Ankle arthritis is a debilitating disease marked by pain and limited function. Total ankle arthroplasty improves pain while preserving motion and offers an alternative to the traditional treatment of ankle fusion. Gait analysis and functional outcomes tools can provide an objective balanced analysis of ankle replacement for the treatment of ankle arthritis. Twenty-nine patients with end-stage ankle arthritis were evaluated before and after ankle arthroplasty. Multi-segment foot and ankle kinematics were assessed annually following surgery (average 3.5 years, range 1-6 years) using the Milwaukee Foot Model and a Vicon video motion analysis system. Functional outcomes (American Orthopedic Foot and Ankle Society [AOFAS] ankle/hindfoot scale, short form 36 [SF-36] questionnaire) and temporal-spatial parameters were also assessed. Kinematic results were compared to findings from a previously collected group of healthy ambulators. AOFAS and SF-36 mean scores improved postoperatively. Walking speed and stride length increased after surgery. There were significant improvements in tibial sagittal range of motion in terminal stance and hindfoot sagittal range of motion in preswing. Decreased external rotation of the tibia and increased external rotation of the hindfoot were noted throughout the gait cycle. Pain and function improved after ankle replacement as supported by better outcomes scores, increased temporal-spatial parameters, and significant improvement in tibial sagittal range of motion during terminal stance and hindfoot sagittal range of motion during preswing. While multi-segment foot kinematics were improved, they were not restored to control values. Statement of clinical significance: Total ankle arthroplasty does not fully normalize mutli-segment gait kinematics despite improved patient-reported outcomes and gait mechanics.

Factors used in Applicant Ranking of Orthopedic Foot and Ankle Fellowships and the Availability of Online Information.

BACKGROUND: The Internet is often the first resource used by applicants to evaluate fellowship programs. However, information on these websites can be often incomplete, inaccessible, and/or inaccurate. The primary objective of this study was to examine key factors that orthopedic foot and ankle fellowship applicants use to rank programs. The secondary objective was to assess both the accessibility and availability of the information on orthopedic foot and ankle fellowship program websites. METHODS: A Qualtrics survey was distributed via e-mail to those who matched into an orthopedic foot and ankle fellowship position from years 2008-2020. A comprehensive list of orthopedic foot and ankle fellowship programs was created. Program websites were evaluated for accessibility as well as the quality of recruitment and educational content. RESULTS: There were a total of 114 survey responses out of 644 invites (17.7%). The most important factors for establishing a rank list were operative experience, current faculty, and program reputation. Eighty-five percent (41/48) of orthopedic foot and ankle fellowship websites were directly accessible using Google. On average, accessible orthopedic foot and ankle fellowship websites contained only 57% (11.5/20) of the content deemed desirable. CONCLUSION: Orthopedic foot and ankle websites are widely accessible and have higher recruitment and educational quality content scores compared with previously published data. The most important factors for establishing a rank list are consistent with previous literature. Those who ranked operative experience as one of the most important factors when establishing a rank list did not complete more operative cases than those who did not. LEVEL OF EVIDENCE: Level IV.