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Background The development of blood-based biomarker tests that are accurate and robust for Alzheimer’s disease (AD) pathology have the potential to aid clinical diagnosis and facilitate enrollment in AD drug trials. We developed a high-resolution mass spectrometry (MS)-based test that quantifies plasma Aβ42 and Aβ40 concentrations and identifies the ApoE proteotype. We evaluated robustness, clinical performance, and commercial viability of this MS biomarker assay for distinguishing brain amyloid status. Methods We used the novel MS assay to analyze 414 plasma samples that were collected, processed, and stored using site-specific protocols, from six independent US cohorts. We used receiver operating characteristic curve (ROC) analyses to assess assay performance and accuracy for predicting amyloid status (positive, negative, and standard uptake value ratio; SUVR). After plasma analysis, sites shared brain amyloid status, defined using diverse, site-specific methods and cutoff values; amyloid PET imaging using various tracers or CSF Aβ42/40 ratio. Results Plasma Aβ42/40 ratio was significantly ( p  < 0.001) lower in the amyloid positive vs. negative participants in each cohort. The area under the ROC curve (AUC-ROC) was 0.81 (95% CI = 0.77–0.85) and the percent agreement between plasma Aβ42/40 and amyloid positivity was 75% at the optimal (Youden index) cutoff value. The AUC-ROC (0.86; 95% CI = 0.82–0.90) and accuracy (81%) for the plasma Aβ42/40 ratio improved after controlling for cohort heterogeneity. The AUC-ROC (0.90; 95% CI = 0.87–0.93) and accuracy (86%) improved further when Aβ42/40, ApoE4 copy number and participant age were included in the model. Conclusions This mass spectrometry-based plasma biomarker test: has strong diagnostic performance; can accurately distinguish brain amyloid positive from amyloid negative individuals; may aid in the diagnostic evaluation process for Alzheimer’s disease; and may enhance the efficiency of enrolling participants into Alzheimer’s disease drug trials.

The diagnostic evaluation for Alzheimer disease may be improved by a blood-based diagnostic test identifying presence of brain amyloid plaque pathology. To determine the clinical performance associated with a diagnostic algorithm incorporating plasma amyloid-β (Aβ) 42:40 ratio, patient age, and apoE proteotype to identify brain amyloid status. This cohort study includes analysis from 2 independent cross-sectional cohort studies: the discovery cohort of the Plasma Test for Amyloidosis Risk Screening (PARIS) study, a prospective add-on to the Imaging Dementia-Evidence for Amyloid Scanning study, including 249 patients from 2018 to 2019, and MissionAD, a dataset of 437 biobanked patient samples obtained at screenings during 2016 to 2019. Data were analyzed from May to November 2020. Amyloid detected in blood and by positron emission tomography (PET) imaging. The main outcome was the diagnostic performance of plasma Aβ42:40 ratio, together with apoE proteotype and age, for identifying amyloid PET status, assessed by accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC). All 686 participants (mean [SD] age 73.2 [6.3] years; 368 [53.6%] men; 378 participants [55.1%] with amyloid PET findings) had symptoms of mild cognitive impairment or mild dementia. The AUC of plasma Aβ42:40 ratio for PARIS was 0.79 (95% CI, 0.73-0.85) and 0.86 (95% CI, 0.82-0.89) for MissionAD. Ratio cutoffs for Aβ42:40 based on the Youden index were similar between cohorts (PARIS: 0.089; MissionAD: 0.092). A logistic regression model (LRM) incorporating Aβ42:40 ratio, apoE proteotype, and age improved diagnostic performance within each cohort (PARIS: AUC, 0.86 [95% CI, 0.81-0.91]; MissionAD: AUC, 0.89 [95% CI, 0.86-0.92]), and overall accuracy was 78% (95% CI, 72%-83%) for PARIS and 83% (95% CI, 79%-86%) for MissionAD. The model developed on the prospectively collected samples from PARIS performed well on the MissionAD samples (AUC, 0.88 [95% CI, 0.84-0.91]; accuracy, 78% [95% CI, 74%-82%]). Training the LRM on combined cohorts yielded an AUC of 0.88 (95% CI, 0.85-0.91) and accuracy of 81% (95% CI, 78%-84%). The output of this LRM is the Amyloid Probability Score (APS). For clinical use, 2 APS cutoff values were established yielding 3 categories, with low, intermediate, and high likelihood of brain amyloid plaque pathology. These findings suggest that this blood biomarker test could allow for distinguishing individuals with brain amyloid-positive PET findings from individuals with amyloid-negative PET findings and serve as an aid for Alzheimer disease diagnosis.

The development of blood-based biomarker tests that are accurate and robust for Alzheimer's disease (AD) pathology have the potential to aid clinical diagnosis and facilitate enrollment in AD drug trials. We developed a high-resolution mass spectrometry (MS)-based test that quantifies plasma A[beta]42 and A[beta]40 concentrations and identifies the ApoE proteotype. We evaluated robustness, clinical performance, and commercial viability of this MS biomarker assay for distinguishing brain amyloid status. We used the novel MS assay to analyze 414 plasma samples that were collected, processed, and stored using site-specific protocols, from six independent US cohorts. We used receiver operating characteristic curve (ROC) analyses to assess assay performance and accuracy for predicting amyloid status (positive, negative, and standard uptake value ratio; SUVR). After plasma analysis, sites shared brain amyloid status, defined using diverse, site-specific methods and cutoff values; amyloid PET imaging using various tracers or CSF A[beta]42/40 ratio. Plasma A[beta]42/40 ratio was significantly (p < 0.001) lower in the amyloid positive vs. negative participants in each cohort. The area under the ROC curve (AUC-ROC) was 0.81 (95% CI = 0.77-0.85) and the percent agreement between plasma A[beta]42/40 and amyloid positivity was 75% at the optimal (Youden index) cutoff value. The AUC-ROC (0.86; 95% CI = 0.82-0.90) and accuracy (81%) for the plasma A[beta]42/40 ratio improved after controlling for cohort heterogeneity. The AUC-ROC (0.90; 95% CI = 0.87-0.93) and accuracy (86%) improved further when A[beta]42/40, ApoE4 copy number and participant age were included in the model. This mass spectrometry-based plasma biomarker test: has strong diagnostic performance; can accurately distinguish brain amyloid positive from amyloid negative individuals; may aid in the diagnostic evaluation process for Alzheimer's disease; and may enhance the efficiency of enrolling participants into Alzheimer's disease drug trials.

Purpose Glenoid augmentation using free bone blocks for anterior shoulder instability has been proposed as an alternative to or bail-out for the Latarjet procedure. The purpose of this investigation was to systematically review and compare outcomes of patients undergoing glenoid augmentation using free bone block autografts versus allografts. Methods A systematic review using PubMed, MEDLINE, Embase, and the Cochrane Library databases was performed in line with the PRISMA statement. Studies reporting outcomes of patients treated with free bone block procedures for anterior shoulder instability with minimum 2-year follow-up were included. Random effects modelling was used to compare patient-reported outcomes, return to sports, recurrent instability, non-instability related complications, and development of arthritis between free bone block autografts and allografts. Results Eighteen studies comprising of 623 patients met the inclusion criteria for this investigation. There were six studies reporting on the use of allografts (of these, two used distal tibial, three iliac crest, and one femoral head allograft) in 173 patients and twelve studies utilizing autografts (of these, ten used iliac crest and two used free coracoid autograft) in 450 patients. Mean age was 28.7 ± 4.1 years for the allograft group and 27.8 ± 3.8 years for the autograft group (n.s). Mean follow-up was 98 months in autograft studies and 50.8 months for allograft studies (range 24–444 months, n.s). Overall mean increase in Rowe score was 56.2 with comparable increases between autografts and allografts (n.s). Pooled recurrent instability rates were 3% (95% CI, 1–7%; I 2  = 77%) and did not differ between the groups (n.s). Arthritic progression was evident in 11% of autografts (95% CI, 2–27%; I 2  = 90%) and 1% (95% CI, 0–8%; I 2  = 63%) of allografts (n.s). The overall incidence of non-instability related complications was 5% (95% CI, 2–10%; I 2  = 81%) and was similar between the groups (n.s). Pooled return to sports rate was 88% (95% CI, 76–96%; I 2  = 76%). Conclusion Glenoid augmentation using free bone block autograft or allograft in the setting of recurrent anterior shoulder instability with glenoid bone loss is effective and safe. Outcomes and complication incidence using autografts and allografts were comparable. Due to the high degree of heterogeneity in the data and outcomes reported in available studies, which consist primarily of retrospective case series, future prospective trials investigating long-term outcomes using free bone block autograft versus allograft for anterior shoulder instability with glenoid bone loss are warranted. Level of evidence IV.

To investigate risk factors for time-loss injuries among soldiers attending U.S. Army Ordnance School Advanced Individual Training. Injuries were obtained from an injury surveillance system. A health questionnaire provided data on age, race, rank, current self-reported injury and illness, and tobacco use. Fitness data was obtained from operations office. Cumulative time-loss injury incidence was 31% for men and 54% for women. For men, higher risk of injury was associated with race, a current self-reported injury, smoking before entering the Army, lower sit-up performance, and slower 2-mile run times. For women, higher risk of injury was associated with race, a current self-reported injury, and slower 2-mile run times. Smoking cessation and fitness training before entry are potential strategies to reduce injuries among soldiers in the Ordnance School.

Injuries and activities associated with injuries were extracted from a retrospective review of the medical records of officers attending the U.S. Army War College during academic years 1999 and 2000 (AY99 and AY00). In AY99, cumulative injury incidence (officers with one or more injuries) was 56%. The next year (AY00), there was command emphasis on injury reduction and education of students on injury prevention strategies. Cumulative injury incidence in AY00 was 44%, significantly lower than in AY99 (p = 0.01, risk ratio [AY99/AY99] = 1.3, 95% confidence interval = 1.1-1.5). Among activities that could be linked to injuries, sports were associated with 41% in AY99 and 45% in AY00. Recommendations for ongoing injury reduction include the following: (1) continued command emphasis and instruction on injury reduction techniques; (2) encouraging the use of semirigid ankle braces to reduce ankle sprains; (3) reducing the number of practice and game sessions in sports activities; (4) encouraging overrunning of second and third base in softball; (5) prohibiting contact with the center line below the net in volleyball; and (6) encouraging medical care providers to record the activity associated with each injury in the medical records.