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OBJECTIVE The evidence on ankylosing spinal disorders (ASDs), including ankylosing spondylitis (AS) and diffuse idiopathic skeletal hyperostosis (DISH), in the context of spinal fracture stems from studies with relatively small sample sizes. There are no studies addressing the patient-reported outcome measures (PROMs) and health-related quality of life (HRQOL) outcomes associated with spinal fracture in this population. The aim of this study was to investigate differences in complications, mortality, PROMs, and HRQOL in patients with and without ASD who had been treated for spinal fracture. METHODS This is a nationwide multicenter retrospective study of prospectively collected data from the Swedish Fracture Register. All patients with fractures of the cervical, thoracic, or lumbar spine treated surgically and conservatively between January 2015 and December 2021 were eligible for inclusion. Two groups of patients were formed based on the presence or absence of concomitant ASD. Primary outcomes of interest included death and PROMs. For surgically treated patients, data on complications and reoperation rates were retrieved. Propensity score matching with a ratio of 1:1 was used to balance the groups prior to intergroup comparison. Variables included in the matching process were age, sex, mechanism of injury, neurological function on admission (Frankel grade), injury type (high vs low energy), fracture type, injured spinal level, time to treatment, and type of treatment (surgical vs conservative). Kaplan-Meier analyses were used to study overall survival following injury. RESULTS A total of 14,604 patients without ASD and 1368 patients with ASD were included in this study. High-energy injuries were less frequent in patients with ASD (13% vs 24%, p < 0.001). Moreover, patients with ASD were less likely to be neurologically intact on admission (90% vs 94%, p < 0.001). There were 1707 surgically treated patients without ASD and 559 with the disorder. After matching, a higher overall risk of reoperation was found among patients with ASD (9.1% vs 3.4%, p = 0.007). Surgical site infections requiring reoperation (p = 0.012), but not construct failure or CSF leakage requiring reoperation (p ≥ 0.05), were more common among the patients with ASD. Postmatching, there were no differences in overall survival between ASD and non-ASD cases (p > 0.05). Moreover, patients with and without ASD had similar PROMs, as indicated by the EQ-5D-3L index at 1 year after injury (p = 0.59). CONCLUSIONS Self-reported recovery 1 year after spinal fracture occurred to a similar extent in patients with and without ASD. Moreover, ASD alone was not a significant risk factor for death. Finally, surgically treated patients with ASD experienced higher rates of postoperative complications and reoperations following surgery.

OBJECTIVE The landscape of healthcare policies has undergone significant reforms, with a notable shift toward a patient-centered basis. This change has prioritized the use of metrics reflecting subjective patient-reported outcome measures (PROMs). However, these metrics are often limited, especially in terms of determining clinically relevant changes over time. The concept of the minimal clinically important difference (MCID) has been introduced to address this limitation. In this study, the authors aimed to assess the predictive capability of relative change and its corresponding threshold value, the minimal clinically important relative change (MCIRC), as an alternative to the absolute difference and MCID. METHODS Prospectively collected data from 2006 to 2021 were obtained from the Swedish Spine Registry (Swespine). PROMs included the numeric rating scale (NRS) neck and arm pain scores, the EQ-5D index and EQ visual analog scale (VAS), and the Neck Disability Index (NDI). Anchor-based methods were used to determine MCID and MCIRC. Absolute differences and relative changes were compared in terms of predictive power using the area under the receiver operating characteristic curve (AUC). RESULTS A total of 5323 patients were included. The chosen MCID values were −3 for NRS neck pain, −3 for NRS arm pain, 0.08 for EQ-5D index, 13 for EQ VAS, and −30 for NDI scores. The chosen MCIRC values were −40% for NRS neck pain, −50% for arm pain, 323% for EQ-5D index, 55% for EQ VAS, and −33% for NDI scores. Relative change was superior for NRS neck and arm pain scores and NDI, while absolute difference was superior for EQ-5D and EQ VAS scores. CONCLUSIONS Relative change and its corresponding MCIRC were found to be more appropriate as a surrogate of subjective satisfaction when studying the NRS and NDI scores, whereas absolute difference and MCID was more appropriate when addressing EQ-5D index and EQ VAS scores.

Objective The objective of this study was to determine the predictive value of amyloid‐positron emission tomography (PET) versus the plasma ratio of phosphorylated tau at threonine 217 (p‐tau217) to non‐phosphorylated tau217 (%p‐tau217) for tau‐PET transitions (T− to T+). The added value of combining plasma amyloid‐β 42 and amyloid‐β 40 (Aβ42/40) and %p‐tau217 into an amyloid probability score (APS2) was also assessed. Methods Mayo Clinic Study of Aging (MCSA) participants had plasma markers measured at via mass spectrometry (MS), an amyloid‐PET scan, and a tau‐PET (meta‐temporal region of interest [ROI]) negative scan (standardized uptake value ratio [SUVR] <1.29) at the index (baseline) date, along with one or more follow‐up tau‐PET scans. The BioFINDER‐2 cohort was used for validation. Cox proportional hazards models adjusted for age, sex, and apolipoprotein ( APOE ) ε4 were used to assess predictors, with scaling to the interquartile range (IQR) for comparability of hazard ratios (HR). Results Among 255 tau‐PET negative MCSA participants (median age: 71.9 years), 37 converted to tau‐PET positive (median follow‐up time: 3.81 years). Higher %p‐tau217 (HR: 1.52 [95% CI: 1.28–1.80]), amyloid‐PET centiloid (HR: 1.47 [95% CI: 1.20–1.79]), and APS2 (HR: 1.62 [95% CI: 1.22–2.16]) predicted tau‐PET conversion. However, Aβ42/40 (HR: 0.94 [95% CI: 0.54–1.66]) was not associated with tau‐PET conversion. In the BioFINDER‐2 cohort (605 tau‐negative, median age: 70.2), 33 converted to tau‐positive (median follow‐up time: 2 years), with higher %p‐tau217 (HR: 1.80 [95% CI: 1.50–2.17]), amyloid‐PET centiloid (HR: 2.29 [95% CI: 1.77–2.97]), and lower Aβ42/40 (HR: 2.38 [95% CI: 1.17–4.83]) predicting conversion. Interpretation In two cohorts, %p‐tau217 was associated with tau‐PET conversion, comparable to amyloid‐PET. APS2 also predicted conversion in the MCSA cohort, whereas Aβ42/40 predicted conversion in the BioFINDER‐2 cohort, which had more individuals with cognitive impairment. ANN NEUROL 2025;98:1249–1260

Abstract INTRODUCTION Plasma biomarkers’ utility for predicting incident mild cognitive impairment (MCI) remains unclear. We evaluated associations of plasma Alzheimer's disease (AD) biomarkers and amyloid positron emission tomography (PET) with transitions from cognitively unimpaired (CU) to MCI in the Mayo Clinic Study of Aging (MCSA) and BioFINDER‐2 studies. METHODS Associations of continuous baseline plasma biomarker levels and amyloid PET Centiloid with progression to MCI, adjusting for age, sex, and education, were evaluated with Cox proportional hazards models. RESULTS The study included 381 MCSA and 584 BioFINDER‐2 participants. Amyloid PET and percent phosphorylated to non‐phosphorylated tau217 (%p‐tau217) were strong predictors of progression to MCI in both cohorts: hazard ratios of 1.49 and 1.23 in the MCSA and 1.72 and 1.65 in BioFINDER, respectively. Amyloid beta 42/40 was a significant predictor in BioFINDER‐2 only (hazard ratio 2.20). DISCUSSION Plasma %p‐tau217 was associated with progression from CU to MCI in both cohorts, although differences in biomarker associations may be related to differences in the two cohorts. Highlights Mass‐spectrometry‐based plasma phosphorylated tau217 was associated with cognitively unimpaired to mild cognitive impairment (MCI) progression. Plasma amyloid beta 42/40 was a significant predictor in BioFINDER but not the Mayo Clinic Study of Aging (MCSA). Amyloid positron emission tomography (PET) was the strongest predictor of progression to MCI in the MCSA. Plasma had added value to amyloid PET in BioFINDER but not the MCSA. Biomarker performance may vary with cohort and biomarker measurement differences.

Abstract Aims Aortic valve-sparing root replacement is recommended over composite root replacement for aortic root aneurysms, especially in younger patients, but long-term outcomes in low-volume nationwide settings remain unclear. The objectives are to compare long-term survival, stroke, and reoperation rates between the two procedures in a low-volume national setting. Methods and results Patients were identified from the Western Danish Heart Registry and the Danish Heart Registry. Cases were validated by review of operative descriptions. The primary outcome was long-term survival from all-cause mortality; secondary outcomes included stroke, reoperation, recurrent aortic regurgitation, and aortic stenosis. Groups were balanced using propensity score matching. Echocardiographic data were provided for the matched cohort. We identified 760 patients treated with composite root replacement and 179 patients with aortic valve-sparing root replacement between January 2010 and April 2022. Mean follow-up was 6.5 years. Composite root replacement patients were younger [50.7 years (SD 14.1) vs. 55.2 (SD 13.5), P &lt; 0.001], but more comorbid with a median EuroSCOREII of 5.5 [interquartile range (IQR): 3.3–11.7] vs. 3.4 (IQR: 2.6–5.0) (P &lt; 0.001). After matching 157 patients per group, aortic valve-sparing root replacement showed improved 10-year survival [91.2%, 95% confidence interval (CI) 82.3–95.8 vs. 80.4%, 95% CI 70.0–87.5, log-rank P = 0.026], with lower 10-year stroke risk (4.9%, 95% CI 1.8–13.0 vs. 18.9%, 95% CI 11.7–29.9, log-rank P = 0.007). Risk of reoperation was nonsignificant (log-rank P = 0.12), which was consistent in the crude population when accounting for competing risk of death (log-rank P = 0.09). Conclusion In this nationwide study, aortic valve-sparing root replacement was associated with better long-term survival and lower stroke risk, supporting its role as a durable surgical option for selected patients.

ABSTRACT Human papillomavirus (HPV) is comprised of >200 genotypes and has an ~8 kb, circular, double-stranded DNA genome. Transmission of HPV occurs through skin-to-skin contact and infection of squamous epithelial cells of cutaneous and mucosal surfaces. HPV genotypes are categorized as low- or high-risk (hrHPV) based on oncogenic potential. There are approximately 14 types of hrHPV that can cause several types of cancer, including HPV-associated oropharyngeal squamous cell carcinoma (HPV(+)OPSCC). Detection of HPV(+)OPSCC is traditionally accomplished using p16 immunohistochemistry (IHC) and HPV-specific testing, either DNA or RNA in situ hybridization (ISH) staining or DNA-based PCR of suspected tumor biopsy tissue. More recently, platelet-poor plasma (PPP) samples from patients with HPV(+)OPSCC have proven useful for detection and quantitation of fragments of HPV circulating tumor DNA (ctDNA). ctDNA has been shown to be useful in determining treatment response and monitoring for disease recurrence. In this study, a novel droplet digital PCR assay (ddPCR) was developed and validated for the detection and quantitation of ctDNA from 5 hrHPV genotypes in PPP. Analytical sensitivity ranged from 7.71 to 19.45 fragments of HPV ctDNA per milliliter of PPP across five hrHPV genotypes. In patients with confirmed primary or recurrent HPV(+)OPSCC or HPV(-)OPSCC, testing of corresponding PPP samples ( n = 32) by ddPCR demonstrated 90.63% (29/32) overall agreement with p16/HPV-ISH biopsy results. Compared with reference ddPCR assays performed at outside laboratories, our ddPCR assay yielded 90% (9/10) overall agreement. This assay may provide clinicians with a tool for monitoring HPV ctDNA prior to, during, and after treatment of an HPV-associated cancer. IMPORTANCE At least 14 genotypes of human papillomavirus (HPV) have been identified to have high oncogenic potential. While molecular diagnostic testing for HPV is widely available for liquid cytologic cervical samples, testing is limited for other sample types, including liquid biopsy samples, such as platelet-poor plasma (PPP). With the rising incidence of HPV-associated oropharyngeal squamous cell carcinoma (HPV(+)OPSCC), laboratory testing is an essential part of patient diagnosis, management, and surveillance. Here, we summarize the development and analytical performance validation of a multiplexed, droplet digital PCR (ddPCR) assay for the detection and quantitation of HPV circulating tumor DNA (ctDNA) in PPP. This assay may provide clinicians with a tool to address minimal residual disease for patients with an HPV-associated cancer.

AbstractIntroductionThis study evaluates the feasibility of utilizing a commercial‐grade 3D LiDAR/RGB camera, combined with 3D reconstruction software, to create an accurate and hyper‐realistic digital model of a proton therapy treatment room. This reconstructed model aims to enhance collision avoidance strategies and improve 3D machine model accessibility. Utilization of a 3D LiDAR/RGB camera as a radiotherapy environment modeling has not been reported prior.MethodsTo create a comprehensive 3D model of a half‐gantry proton therapy system, colored point cloud data was captured using the Matterport Pro 3 camera, a hybrid LiDAR and RGB imaging system with high‐resolution capabilities (134.2 MP), a 360° horizontal field of view, and 20 mm accuracy at 10 m. A total of 117 acquisition points, distributed across the treatment room with three camera heights, ensured complete coverage and minimal occlusions. Scanning, completed in under 3 hours, was monitored in real time using the Matterport App. Post‐scan processing involved denoising and converting the point cloud into 3D mesh structures using MeshLab, followed by refined pair‐wise iterative closest point (ICP) alignments. Textures and materials were assigned to reflect real‐world objects, and a ray‐tracing engine simulated realistic lighting in Blender. Animations illustrating the kinematics of the treatment couch and gantry were simulated in Blender for enhanced visualization.ResultsThe scanning process achieved complete data capture without missing information, attributed to strategic oversampling during data acquisition. The mean root mean square error (RMSE) of the ICP registration was 0.008 m. The validation process confirmed that the dimensions of the treatment couch within the digital model closely matched the actual measurements with less than 2 cm deviation, indicating high accuracy. The resulting digital twin provided a photorealistic and immersive representation of the proton therapy treatment room, serving as a valuable digital asset for various applications.ConclusionIt is possible to generate vendor‐independent and highly accurate 3D models of the proton treatment room environment with a commercial grade LiDAR/RGB camera to expand future research opportunities and education endeavors.

Abstract The link between regional tau load and clinical manifestation of Alzheimer’s disease (AD) highlights the importance of characterizing spatial tau distribution across disease variants. In typical (memory-predominant) AD, the spatial progression of tau pathology mirrors the functional connections from temporal lobe epicentres. However, given the limited spatial heterogeneity of tau in typical AD, atypical (non-amnestic-predominant) AD variants with distinct tau patterns provide a key opportunity to investigate the universality of connectivity as a scaffold for tau progression. In this large-scale, multicentre study across 14 international sites, we included cross-sectional tau-PET data from 320 individuals with atypical AD (n = 139 posterior cortical atrophy/PCA-AD; n = 103 logopenic variant primary progressive aphasia/lvPPA-AD; n = 35 behavioural variant AD/bvAD; n = 43 corticobasal syndrome/CBS-AD), with a subset of individuals (n = 78) having longitudinal tau-PET data. Additionally, as an independent sample, we included regional post-mortem tau stainings from 93 atypical AD patients from two sites (n = 19 PCA-AD, n = 32 lvPPA-AD, n = 23 bvAD, n = 19 CBS-AD). Gaussian mixture modelling was used to harmonize different tau-PET tracers by transforming tau-PET standardized uptake value ratios to tau positivity probabilities (a uniform scale ranging from 0% to 100%). Using linear regression, we assessed whether brain regions with stronger resting-state functional MRI-based functional connectivity, derived from healthy elderly controls in the Alzheimer’s Disease Neuroimaging Initiative (ADNI), showed greater covariance in cross-sectional and longitudinal tau-PET and post-mortem tau pathology. Furthermore, we examined whether functional connectivity of tau-PET epicentres (i.e. the top 5% of regions with the highest baseline tau load) and tau-PET accumulation epicentres (i.e. the top 5% of regions with the highest tau accumulation rates) was associated with cross-sectional and longitudinal tau patterns. Our findings show that tau-PET epicentres aligned with clinical variants, e.g. a visual network predominant pattern in PCA-AD (‘visual AD’) and left-hemispheric temporal predominance, particularly within the language network, in lvPPA-AD (‘language AD’). Moreover, more strongly functionally connected regions showed correlated concurrent tau-PET levels (confirmed with post-mortem data) and tau-PET accumulation rates. The functional connectivity profile of tau-PET epicentres and accumulation epicentres corresponded to tau-PET progression patterns, with higher tau-PET levels and accumulation rates in functionally close regions, and lower tau-PET levels and accumulation rates in functionally distant regions. Our data are consistent with the hypothesis that tau propagation occurs along functional connections originating from local epicentres, across all AD clinical variants. Since tau proteinopathy is a major driver of neurodegeneration and cognitive decline, this finding may advance personalized medicine and participant-specific end points in clinical trials.