Citations

Importance Advances in Alzheimer disease (AD) have shifted research focus to earlier disease stages, necessitating more scalable approaches to identify cognitively unimpaired individuals with amyloid β (Aβ) pathology. Objective To assess the utility of plasma phosphorylated tau 217 (p-tau217) for classifying Aβ status in cognitively unimpaired individuals, both as a stand-alone test and in a 2-step approach where positive plasma results were confirmed using a second modality (Aβ positron emission tomography [PET] or cerebrospinal fluid [CSF]). Design, Setting, and Participants This cross-sectional cohort study used data collected between June 2009 and March 2024. We included 2916 cognitively unimpaired participants from 12 international independent observational cohorts in the US, Europe, Australia, and Canada with available plasma p-tau217 levels and CSF or PET Aβ biomarkers. Performance comparisons between mass spectrometry and immunoassay-based p-tau217 measurements were also performed (n = 964). Exposures Plasma p-tau217 levels measured by immunoassay. Main Outcome and Measures Aβ status, determined by CSF or Aβ PET biomarkers. Results Participants had a mean (SD) age of 66.9 (9.9) years; 971 (33.3%) were Aβ positive by either CSF or PET, 1667 (57.2%) were women, and 1108 (38.1%) carried at least 1 APOE ε4 allele. As a stand-alone test, plasma p-tau217 achieved a positive predictive value (PPV) of 79% (95% CI, 74-84) and an overall accuracy of 81% (95% CI, 80-82). In a 2-step workflow, the PPV and accuracy significantly increased to 91% (95% CI, 86-95). While this approach required screening of 677 individuals with plasma p-tau217 to identify 100 Aβ-positive individuals, compared to 536 participants when using PET alone, it reduced the need for PET testing to 124. Immunoassays demonstrated comparable PPVs to mass spectrometry (80% [95% CI, 74-86] vs 85% [95% CI, 81-90]; P = .12) but significantly lower overall accuracy (82% [95% CI, 79-84]% vs 88 [95% CI, 86-90]; P < .001) and true Aβ-positive detection rate (49% [95% CI, 43-55] vs 69% [95% CI, 64-75]; P < .001). Conclusions and Relevance The findings highlight the potential of plasma p-tau217 as a stand-alone test—or when used in a sequential 2-step approach alongside PET or CSF testing—as a cost-effective, scalable, and minimally burdensome strategy for identifying preclinical AD. Tailored screening workflows that incorporate p-tau217 can improve efficiency in participant selection for preclinical AD trials and, in the future, help guide access to disease-modifying treatments.

Bone health is a key determinant of success in spine surgery, making preoperative assessment of bone quality essential to optimal surgical risk stratification. Magnetic resonance imaging (MRI)-based vertebral bone quality (VBQ) score offers a novel approach to assess bone health in spine surgery candidates. The ability of MRI to assess bone quality without exposure to ionizing radiation makes it a potentially advantageous alternative to other traditional measures of bone density. VBQ has additionally shown potential to predict adverse outcomes, such as fragility fractures, instrumentation failure, subsidence and proximal junctional kyphosis. Variations of VBQ, such as endplate bone quality, S1 VBQ, and cervical VBQ, provide targeted insights at specific anatomical regions and potentially enhance the predictive accuracy of VBQ. However, clinical application of VBQ is limited by variability in MRI systems, patient-specific factors, and lack of standardized threshold values. This review aims to critically evaluate VBQ scores as an opportunistic, MRI-based assessment of bone health and its potential role in predicting surgical outcomes. While VBQ may provide some valuable insights into bone health, its role in preoperative risk assessment likely remains supplementary and requires further research to establish clinical validity and optimal cutoffs.

Abstract Early diagnosis and treatment are essential for improving outcomes of coccidioidal meningitis. While the detection of IgG by serologic testing of the cerebrospinal fluid (CSF) has been a mainstay of diagnosis for years, the diagnosis of coccidioidal meningitis in clinical practice can be very challenging due to suboptimal sensitivity of laboratory tests. We reviewed the results of the CSF diagnostic test results from the initial lumbar puncture in 110 patients with proven, probable, and likely coccidioidal meningitis from 1989 to 2024. One hundred four patients were diagnosed with coccidioidal meningitis on the initial CSF examination. The positivity rate of the first CSF testing was 89.1% (n = 64) for IgG by enzyme immunoassay, 62.2% (n = 98) for IgG by immunodiffusion, and 70.2% (n = 104) for IgG by complement fixation, 4.4% (n = 90) for fungal culture, 18.8% (n = 69) for polymerase chain reaction, and 33% (n = 21) for Coccidioides antigen. The non-specific fungal marker 1,3-β-d-glucan was positive in the CSF in 70.4% (n = 27) of samples. Contrasted brain magnetic resonance imaging identified leptomeningeal enhancement in 53.1%. Optimal detection of coccidioidal meningitis requires a combination of diagnostic modalities.

OBJECTIVE Anterior cervical discectomy and fusion (ACDF) is an established treatment for cervical degenerative disc disease; however, the procedure can cause loss of cervical spine range of motion and potentially accelerate adjacent segment degeneration. Cervical disc arthroplasty (CDA) seeks to preserve native motion of the cervical spine, which can theoretically reduce the incidence of adjacent level degeneration. The literature regarding the relative efficacy of ACDF versus CDA remains inconsistent. In this study, the authors investigate the difference in outcomes between ACDF and CDA and identify factors contributing to the heterogeneity in the literature. METHODS The Ovid, Embase, Scopus, Cochrane, and ClinicalTrials.gov databases were systematically searched from inception to September 5, 2023, for randomized controlled trials (RCTs) comparing ACDF and CDA for degenerative disc disease. Studies were extracted by two authors and verified by a third. Random-effects meta-analysis was performed. The primary outcome was the difference in clinical outcomes between the two surgical groups. The secondary outcomes were the differences in radiological outcomes, surgical characteristics, complication rates, and hospital lengths of stay. The study was registered with the International Prospective Register of Systematic Reviews (PROSPERO; registration no. CRD42023469204) and adhered to the PRISMA guidelines. RESULTS From 584 articles uploaded to the Covidence platform for screening, 35 studies derived from 25 RCTs were included in this systematic review and meta-analysis. A total of 4530 patients were treated with ACDF (2081) and CDA (2449). Forty-six percent of the patients (2063) were male, and the mean age of the study cohort was 45 ± 3 years. In terms of the primary outcome, CDA showed higher rates of neurological and overall success. Regarding the secondary outcomes, CDA demonstrated a significantly lower rate of adjacent level disease, higher rate of heterotopic ossification, and greater range of motion at the operated level. Additionally, CDA had lower rates of reoperation but significantly longer operative times than ACDF. The inclusion of myelopathic patients and variations in follow-up between the surgical groups contributed to the observed effect heterogeneity among studies. CONCLUSIONS In this study, CDA showed comparable or potentially greater success in overall and neurological outcomes, along with a lower incidence of adjacent level degeneration and reoperation rates but longer operative times.

Importance Multiparametric magnetic resonance imaging (MRI), with or without prostate biopsy, has become the standard of care for diagnosing clinically significant prostate cancer. Resource capacity limits widespread adoption. Biparametric MRI, which omits the gadolinium contrast sequence, is a shorter and cheaper alternative offering time-saving capacity gains for health systems globally. Objective To assess whether biparametric MRI is noninferior to multiparametric MRI for diagnosis of clinically significant prostate cancer. Design, Setting, and Participants A prospective, multicenter, within-patient, noninferiority trial of biopsy-naive men from 22 centers (12 countries) with clinical suspicion of prostate cancer (elevated prostate-specific antigen [PSA] level and/or abnormal digital rectal examination findings) from April 2022 to September 2023, with the last follow-up conducted on December 3, 2024. Interventions Participants underwent multiparametric MRI, comprising T2-weighted, diffusion-weighted, and dynamic contrast–enhanced (DCE) sequences. Radiologists reported abbreviated biparametric MRI first (T2-weighted and diffusion-weighted), blinded to the DCE sequence. After unblinding, radiologists reported the full multiparametric MRI. Patients underwent a targeted biopsy with or without systematic biopsy if either biparametric MRI or multiparametric MRI was suggestive of clinically significant prostate cancer. Main outcomes and measures The primary outcome was the proportion of men with clinically significant prostate cancer. Secondary outcomes included the proportion of men with clinically insignificant cancer. The noninferiority margin was 5%. Results Of 555 men recruited, 490 were included for primary outcome analysis. Median age was 65 (IQR, 59-70) years and median PSA level was 5.6 (IQR, 4.4-8.0) ng/mL. The proportion of patients with abnormal digital rectal examination findings was 12.7%. Biparametric MRI was noninferior to multiparametric MRI, detecting clinically significant prostate cancer in 143 of 490 men (29.2%), compared with 145 of 490 men (29.6%) (difference, −0.4 [95% CI, −1.2 to 0.4] percentage points; P = .50). Biparametric MRI detected clinically insignificant cancer in 45 of 490 men (9.2%), compared with 47 of 490 men (9.6%) with the use of multiparametric MRI (difference, −0.4 [95% CI, −1.2 to 0.4] percentage points). Central quality control demonstrated that 99% of scans were of adequate diagnostic quality. Conclusion and relevance In men with suspected prostate cancer, provided image quality is adequate, an abbreviated biparametric MRI scan, with or without targeted biopsy, could become the new standard of care for prostate cancer diagnosis. With approximately 4 million prostate MRIs performed globally annually, adopting biparametric MRI could substantially increase scanner throughput and reduce costs worldwide. Trial registration ClinicalTrials.gov Identifier: NCT04571840

Abstract Repetitive head impacts are associated with structural brain changes and an increased risk for chronic traumatic encephalopathy, a progressive neurodegenerative disease that can only be diagnosed after death. Chronic traumatic encephalopathy is defined by the abnormal accumulation of phosphorylated tau protein, particularly at the depths of the superior frontal sulci, suggesting that sulcal morphology may serve as a relevant structural biomarker. Contact sport athletes, such as former football players, are at elevated risk due to their prolonged exposure to repetitive head impacts. Cortical atrophy linked to underlying tau accumulation may result in shallower and wider sulci, potentially making sulcal morphology an imaging marker for identifying individuals at risk for this disease. This study investigated sulcal morphological differences in former football players and examined associations with age, football-related exposure, clinical diagnosis of traumatic encephalopathy syndrome, levels of certainty for chronic traumatic encephalopathy pathology, neuropsychological performance, and positron emission tomography imaging using flortaucipir. We analysed structural magnetic resonance imaging data from 169 male former football players (mean age 57.2 (8.2) years, range 45–74) and 54 age-matched, unexposed asymptomatic male controls (mean age 59.4 (8.5) years, range 45–74). Sulcal depth and width were quantified using the CalcSulc, focusing on two regions in each hemisphere commonly affected by chronic traumatic encephalopathy pathology: the superior frontal and occipitotemporal sulci. Generalized least squares models were used to assess group differences and interactions with age and football exposure variables, including age of first exposure, total years played, and cumulative head impact exposure. An analysis of covariance evaluated relationships between sulcal morphology, clinical measures, and flortaucipir uptake, adjusting for age, race, body mass index, education, imaging site, apolipoprotein E4 status, and total intracranial volume. Former football players demonstrated significantly shallower sulcal depth in the left superior frontal sulcus compared to unexposed controls. Earlier age of first exposure and longer football careers were associated with greater widening of the left occipitotemporal sulcus. Higher cumulative head impact exposure was linked to reduced sulcal depth in the left superior frontal region. However, sulcal morphology was not associated with clinical diagnosis, levels of certainty, neuropsychological test performance, or flortaucipir imaging. These findings suggest that sulcal morphology may reflect cumulative exposure to repetitive head impacts, particularly in brain regions vulnerable to chronic traumatic encephalopathy pathology. Future ante- and post-mortem validation studies are needed to determine whether sulcal morphology can serve as a reliable in vivo biomarker of risk.

Abstract Home parenteral nutrition (HPN) is a life‐sustaining therapy traditionally used as a bridge to enteral autonomy or intestinal transplantation. Increasingly, it is used for intractable feeding intolerance (IFI), which can occur near the end of life (EOL) in children with severe neurological impairment (SNI). In these cases, HPN use differs from its historical role and requires tailored outpatient planning. We report a retrospective case series of four children with SNI who developed IFI and received HPN as part of their EOL care. The pediatric palliative care team (PPCT) was involved in all cases during HPN decision‐making and planning. The pediatric nutrition support team (PNST) and PPCT collaborated to provide individualized, goal‐directed care. Patients ranged from 1 to 12 years old, with HPN durations between 5 weeks and 2 years. All were enrolled in hospice while receiving HPN. Plans were made through shared decision‐making, reflecting each family's values, and included tailored approaches to laboratory monitoring, febrile episodes, line care, growth assessment, and follow‐up. HPN at EOL requires careful ethical consideration, particularly of autonomy because families often find comfort in providing nutrition. IFI is often unanticipated, and prognoses are uncertain. With the combined expertise of PNST and PPCT, HPN can be used meaningfully at EOL, supporting family values, easing suffering, and creating space for peace and connection.

OBJECTIVE The role of amputation and myoelectric prosthetic fitting for hand function in traumatic pan–brachial plexus injury (pBPI) continues to evolve. This study evaluated the function and activity performance of patients with traumatic pBPI who underwent amputation and prosthetic fitting with a myoelectric prosthesis (MEP) for hand function. METHODS A retrospective analysis of adult patients who underwent elective amputation after sustaining a pBPI followed by MEP for hand function was performed. Demographics, mechanisms of injury, amputation details, and outcomes were collected from medical records. The Disabilities of the Arm, Shoulder and Hand (DASH) outcome measure was used to evaluate the impact of impairment, the visual analog scale (VAS) to assess pain, and the Activities Measure for Upper Limb Amputees (AM-ULA) to determine functional activity performance pre- and post-MEP usage. Follow-up time, prosthesis usage, satisfaction, and site of electrical signal used were recorded. Paired t-tests were used to compare outcomes. RESULTS Twenty-one adult patients with pBPI (90% male, mean age 32 years at the time of BPI) underwent amputations and were fitted with MEPs for hand function controlled by nonintuitive signals. Fifteen patients underwent a trans-radial amputation and 6 underwent a trans-humeral amputation. While all patients sought improved terminal grasp function, 3 patients subsequently declined prosthetic fitting after amputation. Of the 18 patients who underwent myoelectric prosthetic hand fittings, linear transducers activated by the contralateral shoulder protraction were used in 66% of patients, and traditional electrode signals from ipsilateral nonintuitive muscle were used in 33% to control MEP grasp function. Disability (DASH) and pain (VAS) scores significantly improved after amputation (p = 0.04 and p < 0.01, respectively). AM-ULA scores showed a significant improvement in activity performance after application of the MEP, with an average increase of 23 points from 0 points on a 40-point scale before amputation and prosthetic fitting (p < 0.0001). Daily users of the MEP averaged 6 hours per day and reported the prosthesis was useful during daily activities with great satisfaction at an average of 22 months of follow-up. CONCLUSIONS Amputation followed by MEP fitting in adult traumatic pBPI significantly improved function, reduced pain, and had a high prosthetic usage. The AM-ULA, a tool for quantitatively evaluating activity performance, was applied to measure the bimanual functional activity performance of patients before and after using MEPs, which revealed a significant improvement. Patients reported using their prosthetics daily with a high satisfaction rate with functional terminal grasp and release.

This study presents the first in vivo intraoperative measurement of the kinetic properties of spastic human muscle. Despite slower relaxation in spastic biceps, the force-frequency relationship was similar to that of the healthy gracilis muscle. This suggests that spasticity does not substantially alter frequency-dependent force summation, possibly due to similar fiber-type compositions and limited changes in calcium handling or myosin isoforms in human spastic muscle.

Abstract In March of 2025, 145 attendees convened at the Hub for Clinical Collaboration of the Children's Hospital of Philadelphia for the inaugural International Society for Magnetic Resonance in Medicine (ISMRM) Body MRI Study Group workshop entitled “Body MRI: Unsolved Problems and Unmet Needs.” Approximately 24% of the attendees were MD or MD/PhD's, 45% were PhD's, and 30% were early‐career trainees and postdoctoral associates. Among the invited speakers and moderators, 28% were from outside the United States, with a 40:60% female‐to‐male ratio. The 2.5‐day program brought together a multidisciplinary group of scientists, radiologists, technologists, and trainees. Session topics included quantitative imaging biomarkers, low‐ and high‐field strengths, artifact and motion correction, rapid imaging and focused protocols, and artificial intelligence. Another key session focused on the importance of team science and allowed speakers from academia and industry to share their personal experiences and offer advice on how to successfully translate new MRI technology into clinical practice. This article summarizes key points from the event and perceived unmet clinical needs within the field of body MRI.