Deep learning to assess bone quality from panoramic radiographs: the feasibility of clinical application through comparison with an implant surgeon and cone-beam computed tomography.

PURPOSE: Bone quality is one of the most important clinical factors for the primary stability and successful osseointegration of dental implants. This preliminary pilot study aimed to evaluate the clinical applicability of deep learning (DL) for assessing bone quality using panoramic (PA) radiographs compared with an implant surgeon's subjective tactile sense and cone-beam computed tomography (CBCT) values. METHODS: In total, PA images of 2,270 edentulous sites for implant placement were selected, and the corresponding CBCT relative gray value measurements and bone quality classification were performed using 3-dimensional dental image analysis software. Based on the pre-trained and fine-tuned ResNet-50 architecture, the bone quality classification of PA images was classified into 4 levels, from D1 to D4, and Spearman correlation analyses were performed with the implant surgeon's tactile sense and CBCT values. RESULTS: The classification accuracy of DL was evaluated using a test dataset comprising 454 cropped PA images, and it achieved an area under the receiving characteristic curve of 0.762 (95% confidence interval [CI], 0.714-0.810). Spearman correlation analysis of bone quality showed significant positive correlations with the CBCT classification (r=0.702; 95% CI, 0.651-0.747; P<0.001) and the surgeon's tactile sense (r=0.658; 95% CI, 0.600-0.708, P<0.001) versus the DL classification. CONCLUSIONS: DL classification using PA images showed a significant and consistent correlation with CBCT classification and the surgeon's tactile sense in classifying the bone quality at the implant placement site. Further research based on high-quality quantitative datasets is essential to increase the reliability and validity of this method for actual clinical applications.

Postoperative Long-Term Monitoring of Mechanical Characteristics in Reconstructed Soft Tissues Using Biocompatible, Immune-Tolerant, and Wireless Electronic Sutures.

Accurate postoperative assessment of varying mechanical properties is crucial for customizing patient-specific treatments and optimizing rehabilitation strategies following Achilles tendon (AT) rupture and reconstruction surgery. This study introduces a wireless, chip-less, and immune-tolerant in vivo strain-sensing suture designed to continuously monitor mechanical stiffness variations in the reconstructed AT throughout the healing process. This innovative sensing suture integrates a standard medical suturing thread with a wireless fiber strain-sensing system, which incorporates a fiber strain sensor and a double-layered inductive coil for wireless readout. The winding design of Au nanoparticle-based fiber electrodes and a hollow core contribute to the fiber strain sensor's high sensitivity (factor of 6.2 and 15.1 pF for revised sensitivity), negligible hysteresis, and durability over 10,000 stretching cycles. To ensure biocompatibility and immune tolerance during extended in vivo periods, an antibiofouling lubricant layer was applied to the sensing suture. Using this sensing system, we successfully monitored the strain responses of the reconstructed AT in an in vivo porcine model. This facilitated the postoperative assessment of mechanical stiffness variations through a well-established analytical model during the healing period.

α-Synuclein seed amplification assay detects Lewy body co-pathology in autosomal dominant Alzheimer's disease late in the disease course and dependent on Lewy pathology burden.

INTRODUCTION: Amyloid beta and tau pathology are the hallmarks of sporadic Alzheimer's disease (AD) and autosomal dominant AD (ADAD). However, Lewy body pathology (LBP) is found in ≈ 50% of AD and ADAD brains. METHODS: Using an α-synuclein seed amplification assay (SAA) in cerebrospinal fluid (CSF) from asymptomatic (n = 26) and symptomatic (n = 27) ADAD mutation carriers, including 12 with known neuropathology, we investigated the timing of occurrence and prevalence of SAA positive reactivity in ADAD in vivo. RESULTS: No asymptomatic participant and only 11% (3/27) of the symptomatic patients tested SAA positive. Neuropathology revealed LBP in 10/12 cases, primarily affecting the amygdala or the olfactory areas. In the latter group, only the individual with diffuse LBP reaching the neocortex showed α-synuclein seeding activity in CSF in vivo. DISCUSSION: Results suggest that in ADAD LBP occurs later than AD pathology and often as amygdala- or olfactory-predominant LBP, for which CSF α-synuclein SAA has low sensitivity. HIGHLIGHTS: Cerebrospinal fluid (CSF) real-time quaking-induced conversion (RT-QuIC) detects misfolded α-synuclein in ≈ 10% of symptomatic autosomal dominant Alzheimer's disease (ADAD) patients. CSF RT-QuIC does not detect α-synuclein seeding activity in asymptomatic mutation carriers. Lewy body pathology (LBP) in ADAD mainly occurs as olfactory only or amygdala-predominant variants. LBP develops late in the disease course in ADAD. CSF α-synuclein RT-QuIC has low sensitivity for focal, low-burden LBP.

Comparison of tau spread in people with Down syndrome versus autosomal-dominant Alzheimer's disease: a cross-sectional study.

BACKGROUND: In people with genetic forms of Alzheimer's disease, such as in Down syndrome and autosomal-dominant Alzheimer's disease, pathological changes specific to Alzheimer's disease (ie, accumulation of amyloid and tau) occur in the brain at a young age, when comorbidities related to ageing are not present. Studies including these cohorts could, therefore, improve our understanding of the early pathogenesis of Alzheimer's disease and be useful when designing preventive interventions targeted at disease pathology or when planning clinical trials. We compared the magnitude, spatial extent, and temporal ordering of tau spread in people with Down syndrome and autosomal-dominant Alzheimer's disease. METHODS: In this cross-sectional observational study, we included participants (aged ≥25 years) from two cohort studies. First, we collected data from the Dominantly Inherited Alzheimer's Network studies (DIAN-OBS and DIAN-TU), which include carriers of autosomal-dominant Alzheimer's disease genetic mutations and non-carrier familial controls recruited in Australia, Europe, and the USA between 2008 and 2022. Second, we collected data from the Alzheimer Biomarkers Consortium-Down Syndrome study, which includes people with Down syndrome and sibling controls recruited from the UK and USA between 2015 and 2021. Controls from the two studies were combined into a single group of familial controls. All participants had completed structural MRI and tau PET (18F-flortaucipir) imaging. We applied Gaussian mixture modelling to identify regions of high tau PET burden and regions with the earliest changes in tau binding for each cohort separately. We estimated regional tau PET burden as a function of cortical amyloid burden for both cohorts. Finally, we compared the temporal pattern of tau PET burden relative to that of amyloid. FINDINGS: We included 137 people with Down syndrome (mean age 38·5 years [SD 8·2], 74 [54%] male, and 63 [46%] female), 49 individuals with autosomal-dominant Alzheimer's disease (mean age 43·9 years [11·2], 22 [45%] male, and 27 [55%] female), and 85 familial controls, pooled from across both studies (mean age 41·5 years [12·1], 28 [33%] male, and 57 [67%] female), who satisfied the PET quality-control procedure for tau-PET imaging processing. 134 (98%) people with Down syndrome, 44 (90%) with autosomal-dominant Alzheimer's disease, and 77 (91%) controls also completed an amyloid PET scan within 3 years of tau PET imaging. Spatially, tau PET burden was observed most frequently in subcortical and medial temporal regions in people with Down syndrome, and within the medial temporal lobe in people with autosomal-dominant Alzheimer's disease. Across the brain, people with Down syndrome had greater concentrations of tau for a given level of amyloid compared with people with autosomal-dominant Alzheimer's disease. Temporally, increases in tau were more strongly associated with increases in amyloid for people with Down syndrome compared with autosomal-dominant Alzheimer's disease. INTERPRETATION: Although the general progression of amyloid followed by tau is similar for people Down syndrome and people with autosomal-dominant Alzheimer's disease, we found subtle differences in the spatial distribution, timing, and magnitude of the tau burden between these two cohorts. These differences might have important implications; differences in the temporal pattern of tau accumulation might influence the timing of drug administration in clinical trials, whereas differences in the spatial pattern and magnitude of tau burden might affect disease progression. FUNDING: None.

High Performance Proprioceptive Fiber Actuators Based on Ag Nanoparticles-Incorporated Hybrid Twisted and Coiled System.

Thermally driven fiber actuators are emerging as promising tools for a range of robotic applications, encompassing soft and wearable robots, muscle function restoration, assistive systems, and physical augmentation. Yet, to realize their full potential in practical applications, several challenges, such as a high operational temperature, incorporation of intrinsic self-sensing capabilities for closed-loop feedback control, and reliance on bulky, intricate actuation systems, must be addressed. Here, an Ag nanoparticles-based twisted and coiled fiber actuator that achieves a high contractile actuation of ≈36% is reported at a considerably low operational temperature of ≈83 °C based on a synergistic effect of constituent fiber elements with low glass transition temperatures. The fiber actuator can monitor its contractile actuation in real-time based on the piezoresistive properties inherent to its Ag-based conductive region, demonstrating its proprioceptive sensing capability. By exploiting this capability, the proprioceptive fiber actuator adeptly maintains its intended contractile behavior, even when faced with unplanned external disturbances. To demonstrate the capabilities of the fiber actuator, this study integrates it into a closed-loop feedback-controlled bionic arm as an artificial muscle, offering fresh perspectives on the future development of intelligent wearable devices and soft robotic systems.

Profilometric, esthetic, and patient-reported outcomes of the L-shape technique combined with delayed connective tissue grafting in the maxillary anterior region: A 3-year case series study.

OBJECTIVE: To evaluate the profilometric, esthetic, and patient-reported outcomes of peri-implant tissues in the maxillary anterior esthetic zone following guided bone regeneration (GBR) using the L-shape technique combined with delayed connective tissue grafting (CTG). MATERIALS AND METHODS: Profilometric and pink esthetic score (PES) measurements were performed at the time of implant surgery with GBR (T0) and at the 1- (T1), 2- (T2), and 3-year (T3) follow-up. Patient-reported outcomes were also assessed using the Oral Health Impact Profile-14 (OHIP-14) questionnaire. Statistical analysis over 3 years of follow-up assessed changes at time points (T0, T1, T2, and T3) and time periods (T0-T1, T0-T2, and T0-T3) using the Wilcoxon signed-rank test. RESULTS: A total of 12 patients (57.5 ± 12.3 years) were included in this study. The mean profilometric change in peri-implant tissues over the 3-year follow-up period was 3.49 ± 1.11 mm, and the buccal contours were not significantly different between the comparison periods. The PES remained stable, while all OHIP-14 domain scores improved significantly. CONCLUSION: Simultaneous implant placement and GBR using the L-shape technique combined with delayed CTG in the maxillary anterior region provides stable buccal profiles and consistent esthetics and improves patient-reported quality of life over a 3-year period. CLINICAL SIGNIFICANCE: This study demonstrated that GBR using the L-shape technique combined with delayed CTG in the maxillary anterior region improved the buccal profile, esthetics, and patient-reported quality of life.

One-Year Longitudinal Changes in Tau Accumulation on [18F]PI-2620 PET in the Alzheimer Spectrum.

We investigated the longitudinal changes in cortical tau accumulation and their association with cognitive decline in patients in the Alzheimer disease (AD) continuum using 2-(2-([18F]fluoro)pyridin-4-yl)-9H-pyrrolo[2,3-b:4,5c']dipyridine ([18F]PI-2620) PET. Methods: We prospectively enrolled 52 participants (age, 69.7 ± 8.4 y; 18 men and 34 women): 7 with normal cognition, 28 with mild cognitive impairment, and 17 with AD. They all completed the [18F]PI-2620 and [18F]florbetaben PET, MRI, and neuropsychologic tests at baseline and, excepting the [18F]florbetaben PET, at the 1-y follow-up. Amyloid-ß (Aß) PET images were visually scored as positive (+) or negative (-). Patients on the AD continuum, including Aß+ mild cognitive impairment and AD, were classified into early-onset (EO+) (<65 y old) or late-onset (LO+) (≥65 y old) groups. [18F]PI-2620 PET SUV ratios (SUVRs) were determined by calculating the cerebral-to-inferior cerebellar ratio. Cortical volumes were calculated using 3-dimensional T1-weighted MRI. The correlation between tau accumulation progression and cognitive decline was also investigated. Results: The global [18F]PI-2620 PET SUVRs were 1.04 ± 0.07 in 15 Aß- patients, 1.18 ± 0.21 in 20 LO+ patients (age, 76.7 ± 3.8 y), and 1.54 ± 0.38 in 17 EO+ patients (age, 63.4 ± 5.4 y; P < 0.001) at baseline. The global SUVR increased over 1 y by 0.05 ± 0.07 (3.90%) and 0.13 ± 0.22 (8.41%) in the LO+ and EO+ groups, respectively, whereas in the Aß- groups, it remained unchanged. The EO+ group showed higher global and regional tau deposition than did the Aß- and LO+ groups (P < 0.05 for each) and rapid accumulation in Braak stage V (0.15 ± 0.25; 9.10% ± 12.27%; P = 0.016 and 0.008), Braak stage VI (0.08 ± 0.12; 7.16% ± 10.06%; P < 0.006 and 0.005), and global SUVR (P = 0.013) compared with the Aß- group. In the EO+ group, the changes in SUVR in Braak stages II-VI were strongly correlated with the baseline and changes in verbal memory (P < 0.03). The LO+ group showed higher tau accumulation in Braak stage I-IV areas than did the Aß- group (P < 0.001 for each). In the LO+ group, the change in SUVR in Braak stages III and IV moderately correlated with the change in attention (P < 0.05), and the change in SUVR in Braak stages V and VI moderately correlated with the change in visuospatial function (P < 0.005). Conclusion: These findings suggest that [18F]PI-2620 PET can be a biomarker to provide regional and chronologic information about tau pathology in the AD continuum.

Development of statistical auto-segmentation method for diffusion restriction gray matter lesions in patients with newly diagnosed sporadic Creutzfeldt-Jakob disease.

Quantification of diffusion restriction lesions in sporadic Creutzfeldt-Jakob disease (sCJD) may provide information of the disease burden. We aim to develop an automatic segmentation model for sCJD and to evaluate the volume of disease extent as a prognostic marker for overall survival. Fifty-six patients (mean age ± SD, 61.2 ± 9.9 years) were included from February 2000 to July 2020. A threshold-based segmentation was used to obtain abnormal signal intensity masks. Segmented volumes were compared with the visual grade. The Dice similarity coefficient was calculated to measure the similarity between the automatic vs. manual segmentation. Cox proportional hazards regression analysis was performed to evaluate the volume of disease extent as a prognostic marker. The automatic segmentation showed good correlation with the visual grading. The cortical lesion volumes significantly increased as the visual grade aggravated (extensive: 112.9 ± 73.2; moderate: 45.4 ± 30.4; minimal involvement: 29.6 ± 18.1 mm3) (P < 0.001). The deep gray matter lesion volumes were significantly higher for positive than for negative involvement of the deep gray matter (5.6 ± 4.6 mm3 vs. 1.0 ± 1.3 mm3, P < 0.001). The mean Dice similarity coefficients were 0.90 and 0.94 for cortical and deep gray matter lesions, respectively. However, the volume of disease extent was not associated with worse overall survival (cortical extent: P = 0.07; deep gray matter extent: P = 0.12).

The impact of alcohol consumption on hearing loss in male workers with a focus on alcohol flushing reaction: the Kangbuk Samsung Cohort Study.

Background: Despite hearing loss being a prevalent chronic condition, estimated to nearly 20% of the global population by the World Health Organization, the specific association with individual lifestyle factors, particularly alcohol consumption, remains unclear. In South Korea, approximately 80% of the population engages in alcohol consumption, with a notably high prevalence among males, indicating a high-risk drinking pattern. Therefore, this study aimed to assess the correlation between alcohol consumption and hearing loss in male workers, as well as to analyze additional variables such as alcohol flushing reaction, with the intention of improving worker health. Methods: The study was conducted from January 2012 to December 2019, targeting 114,114 participants who visited Kangbuk Samsung Hospital Total Healthcare Centers. Data were collected through pure-tone audiometry tests and alcohol-related questionnaire, and statistical analysis was performed using Cox regression analysis. Based on previous studies indicating a potential protective effect of light drinking on hearing loss, this group was designated as the reference. Additionally, stratified analyses were conducted based on the presence of alcohol flushing reaction and different working hours. Results: The hazard ratio (95% confidence interval) for hearing loss was higher in the heavy drinking group (1.23 [1.11-1.37]) compared to the moderate drinking group (1.09 [0.98-1.20]). Stratified analyses revealed a significantly elevated the hazard ratio of hearing loss in groups with alcohol flushing reaction compared to those without this factor. Conclusions: Our study demonstrated that moderate or heavy alcohol consumption in male workers can increase the risk of hearing loss, particularly in those with alcohol flushing reaction. These findings underscore the importance of addressing alcohol-related factors concerning hearing health among male workers.

Long-term results of regenerative treatment of intrabony defects: a cohort study with 5-year follow-up.

BACKGROUND: The aim of this retrospective cohort study was to evaluate the long-term clinical and radiographic outcomes and survival of teeth in periodontal regenerative treatment of intrabony defects using combined enamel matrix protein derivative (EMD) and deproteinized porcine bone mineral (DPBM) compared to EMD alone. METHODS: A total of 333 intrabony defects in 176 patients (mean age: 54.7 ± 8.9 years) were followed-up for 58.6 ± 11.2 (range, 25-78) months after periodontal regenerative treatment. Changes in clinical (pocket probing depth and clinical attachment level) and radiographic (defect depth and defect width) parameters were analyzed using serial periapical radiographs. Kaplan-Meier and multivariate Cox proportional-hazards regression analyses for tooth loss were also performed. RESULTS: Compared to periodontal surgery with EMD alone with a mean follow-up of 5 years, combined EMD and DPBM showed significantly better gain in clinical attachment level (EMD and DPBM: 2.8 ± 2.3 mm vs. EMD alone: 2.2 ± 2.2 mm) and reduction in probing pocket depth (EMD and DPBM: 2.8 ± 1.8 mm vs. EMD alone: 2.3 ± 1.8 mm), defect depth (EMD and DPBM: 2.5 ± 2.4 mm vs. EMD alone: 2.0 ± 2.4 mm) and defect width (EMD and DPBM: 0.6 ± 1.0 mm vs. EMD alone: 0.2 ± 1.3 mm). The overall survival rates of the teeth were 91.48% and 95.20% in the patient- and tooth-based analyses, respectively, showing no statistically significant difference. CONCLUSIONS: Within the limitations of the current study, combined EMD and DPBM offered additional clinical and radiographic benefits over a mean of 5 years compared to EMD alone. However, tooth loss did not differ significantly between the two groups. CLINICAL RELEVANCE: Compared to EMD alone, combined EMD and DPBM for intrabony defects has additional clinical advantages; however, patient- and tooth-related risk factors must be considered when performing periodontal regenerative surgery.

Deep-learning performance in identifying and classifying dental implant systems from dental imaging: a systematic review and meta-analysis.

Deep learning (DL) offers promising performance in computer vision tasks and is highly suitable for dental image recognition and analysis. We evaluated the accuracy of DL algorithms in identifying and classifying dental implant systems (DISs) using dental imaging. In this systematic review and meta-analysis, we explored the MEDLINE/PubMed, Scopus, Embase, and Google Scholar databases and identified studies published between January 2011 and March 2022. Studies conducted on DL approaches for DIS identification or classification were included, and the accuracy of the DL models was evaluated using panoramic and periapical radiographic images. The quality of the selected studies was assessed using QUADAS-2. This review was registered with PROSPERO (CRDCRD42022309624). From 1,293 identified records, 9 studies were included in this systematic review and meta-analysis. The DL-based implant classification accuracy was no less than 70.75% (95% confidence interval [CI], 65.6%-75.9%) and no higher than 98.19 (95% CI, 97.8%-98.5%). The weighted accuracy was calculated, and the pooled sample size was 46,645, with an overall accuracy of 92.16% (95% CI, 90.8%-93.5%). The risk of bias and applicability concerns were judged as high for most studies, mainly regarding data selection and reference standards. DL models showed high accuracy in identifying and classifying DISs using panoramic and periapical radiographic images. Therefore, DL models are promising prospects for use as decision aids and decision-making tools; however, there are limitations with respect to their application in actual clinical practice.

Low- or standard-dose edoxaban versus antiplatelet therapy for leaflet thrombus and cerebral thromboembolism after TAVR: A prespecified analysis of randomized ADAPT-TAVR trial.

BACKGROUND: The risks of leaflet thrombosis and the associated cerebral thromboembolism are unknown according to different anticoagulation dosing after transcatheter aortic valve replacement (TAVR). The aim was to evaluate the incidence of leaflet thrombosis and cerebral thromboembolism between low-dose (30 mg) or standard-dose (60 mg) edoxaban and dual antiplatelet therapy (DAPT) after TAVR. METHODS: In this prespecified subgroup analysis of the ADAPT-TAVR trial, the primary endpoint was the incidence of leaflet thrombosis on 4-dimensional computed tomography at 6-months. Key secondary endpoints were new cerebral lesions on brain magnetic resonance imaging and neurological and neurocognitive dysfunction. RESULTS: Of 229 patients enrolled in this study, 118 patients were DAPT group and 111 were edoxaban group (43 [39.1%] 60 mg vs 68 [61.3%] 30 mg). There was a significantly lower incidence of leaflet thrombosis in the standard-dose edoxaban group than in the DAPT group (2.4% vs 18.3%; odds ratio [OR] 0.11; 95% confidence interval [CI], 0.01-0.55; P = .03). However, no significant difference was observed between low-dose edoxaban and DAPT (15.0% vs 18.3%; OR 0.79; 95% CI, 0.32-1.81; P = .58). Irrespective of different antithrombotic regiments, the percentages of patients with new cerebral lesions on brain MRI and worsening neurological or neurocognitive function were not significantly different. CONCLUSIONS: In patients without an indication for anticoagulation after TAVR, the incidence of leaflet thrombosis was significantly lower with standard-dose edoxaban but not with low-dose edoxaban, as compared with DAPT. However, this differential effect of edoxaban on leaflet thrombosis was not associated with a reduction of new cerebral thromboembolism and neurological dysfunction.

Corrigendum: Development and validation of a deep learning-based automatic segmentation model for assessing intracranial volume: comparison with NeuroQuant, FreeSurfer, and SynthSeg.

[This corrects the article DOI: 10.3389/fneur.2023.1221892.].

Relationship between disproportionately enlarged subarachnoid-space hydrocephalus and white matter tract integrity in normal pressure hydrocephalus.

Normal pressure hydrocephalus (NPH) patients had altered white matter tract integrities on diffusion tensor imaging (DTI). Previous studies suggested disproportionately enlarged subarachnoid space hydrocephalus (DESH) as a prognostic sign of NPH. We examined DTI indices in NPH subgroups by DESH severity and clinical symptoms. This retrospective case-control study included 33 NPH patients and 33 age-, sex-, and education-matched controls. The NPH grading scales (0-12) were used to rate neurological symptoms. Patients with NPH were categorized into two subgroups, high-DESH and low-DESH groups, by the average value of the DESH scale. DTI indices, including fractional anisotropy, were compared across 14 regions of interest (ROIs). The high-DESH group had increased axial diffusivity in the lateral side of corona radiata (1.43 ± 0.25 vs. 1.72 ± 0.25, p = 0.04), and showed decreased fractional anisotropy and increased mean, and radial diffusivity in the anterior and lateral sides of corona radiata and the periventricular white matter surrounding the anterior horn of lateral ventricle. In patients with a high NPH grading scale, fractional anisotropy in the white matter surrounding the anterior horn of the lateral ventricle was significantly reduced (0.36 ± 0.08 vs. 0.26 ± 0.06, p = 0.03). These data show that DESH may be a biomarker for DTI-detected microstructural alterations and clinical symptom severity.

Magnetic resonance image-based brain age as a discriminator of dementia conversion in patients with amyloid-negative amnestic mild cognitive impairment.

Patients with amyloid-negative amnestic mild cognitive impairment (MCI) have a conversion rate of approximately 10% to dementia within 2 years. We aimed to investigate whether brain age is an important factor in predicting conversion to dementia in patients with amyloid-negative amnestic MCI. We conducted a retrospective cohort study of patients with amyloid-negative amnestic MCI. All participants underwent detailed neuropsychological evaluation, brain magnetic resonance imaging (MRI), and [18F]-florbetaben positron emission tomography. Brain age was determined by the volumetric assessment of 12 distinct brain regions using an automatic segmentation software. During the follow-up period, 38% of the patients converted from amnestic MCI to dementia. Further, 73% of patients had a brain age greater than their actual chronological age. When defining 'survival' as the non-conversion of MCI to dementia, these groups differed significantly in survival probability (p = 0.036). The low-educated female group with a brain age greater than their actual age had the lowest survival rate among all groups. Our findings suggest that the MRI-based brain age used in this study can contribute to predicting conversion to dementia in patients with amyloid-negative amnestic MCI.

Frequency, Predictors, and Clinical Impact of Valvular and Perivalvular Thrombus After Transcatheter Aortic Valve Replacement.

BACKGROUND: Subclinical aortic valve complex (valvular and perivalvular) thrombus is not rare after transcatheter aortic valve replacement (TAVR). The risk factors and clinical implications of these findings remain uncertain. OBJECTIVES: This study sought to evaluate the frequency, predictors, and clinical outcome of aortic valve complex thrombus after TAVR. METHODS: In the ADAPT-TAVR (Anticoagulation Versus Dual Antiplatelet Therapy for Prevention of Leaflet Thrombosis and Cerebral Embolization After Transcatheter Aortic Valve Replacement) trial comparing edoxaban vs dual antiplatelet therapy in TAVR patients without an indication for chronic anticoagulation, the frequency of valvular (subclinical leaflet thrombus) and perivalvular (supravalvular, subvalvular, and sinus of Valsalva) thrombus was evaluated by 4-dimensional computed tomography at 6 months. The association of these phenomena with new cerebral thromboembolism on brain magnetic resonance imaging, neurologic and neurocognitive dysfunction, and clinical outcomes was assessed. RESULTS: Among 211 patients with 6-month computed tomography evaluations, 91 patients (43.1%) had thrombus at any aortic valve complex, 30 (14.2%) patients had leaflet thrombus, and 78 (37.0%) patients had perivalvular thrombus. A small maximum diameter of the stent at the valve level and low body surface area were independent predictors of aortic valve complex and perivalvular thrombus, and decreased renal function was an independent predictor of leaflet thrombus. No significant differences were observed in new cerebral lesions, neurologic or neurocognitive functions, or clinical outcomes among patients with or without valvular or perivalvular thrombus. CONCLUSIONS: Subclinical aortic valve complex (valvular and perivalvular) thrombus was common in patients who had undergone successful TAVR. However, these imaging phenomena were not associated with new cerebral thromboembolism, neurologic or neurocognitive dysfunction, or adverse clinical outcomes. (Anticoagulation Versus Dual Antiplatelet Therapy for Prevention of Leaflet Thrombosis and Cerebral Embolization After Transcatheter Aortic Valve Replacement [ADAPT-TAVR]; NCT03284827).

Advanced structural brain aging in preclinical autosomal dominant Alzheimer disease.

BACKGROUND: "Brain-predicted age" estimates biological age from complex, nonlinear features in neuroimaging scans. The brain age gap (BAG) between predicted and chronological age is elevated in sporadic Alzheimer disease (AD), but is underexplored in autosomal dominant AD (ADAD), in which AD progression is highly predictable with minimal confounding age-related co-pathology. METHODS: We modeled BAG in 257 deeply-phenotyped ADAD mutation-carriers and 179 non-carriers from the Dominantly Inherited Alzheimer Network using minimally-processed structural MRI scans. We then tested whether BAG differed as a function of mutation and cognitive status, or estimated years until symptom onset, and whether it was associated with established markers of amyloid (PiB PET, CSF amyloid-ß-42/40), phosphorylated tau (CSF and plasma pTau-181), neurodegeneration (CSF and plasma neurofilament-light-chain [NfL]), and cognition (global neuropsychological composite and CDR-sum of boxes). We compared BAG to other MRI measures, and examined heterogeneity in BAG as a function of ADAD mutation variants, APOE Îµ4 carrier status, sex, and education. RESULTS: Advanced brain aging was observed in mutation-carriers approximately 7 years before expected symptom onset, in line with other established structural indicators of atrophy. BAG was moderately associated with amyloid PET and strongly associated with pTau-181, NfL, and cognition in mutation-carriers. Mutation variants, sex, and years of education contributed to variability in BAG. CONCLUSIONS: We extend prior work using BAG from sporadic AD to ADAD, noting consistent results. BAG associates well with markers of pTau, neurodegeneration, and cognition, but to a lesser extent, amyloid, in ADAD. BAG may capture similar signal to established MRI measures. However, BAG offers unique benefits in simplicity of data processing and interpretation. Thus, results in this unique ADAD cohort with few age-related confounds suggest that brain aging attributable to AD neuropathology can be accurately quantified from minimally-processed MRI.

Association between shift work and the risk of hypothyroidism in adult male workers in Korea: a cohort study.

Background: Shift work has been reported to have several harmful effects on the human body. However, a small number of studies have evaluated the association between shift work and adverse effects on the thyroid. In our longitudinal study, we examined the causal association between shift work and the risk of hypothyroidism. Methods: A Kangbuk Samsung Cohort Study was conducted on 112,648 men without thyroid disease at baseline who were followed up at least once between 2012 and 2019. Shift work status and shift schedule types were categorized using standardized questionnaires. Hypothyroidism was defined using the reference ranges of serum thyroid-stimulating hormones and free thyroxine levels. Hazard ratios (HRs) and 95% confidence intervals (CIs) for incident hypothyroidism were estimated using Cox proportional hazards regression analyses with the daytime work group as the reference. Results: During the 501,237 person-years of follow-up, there were 6,306 incident cases of hypothyroidism (incidence density, 1.26 per 100 person-years). The multivariable-adjusted HR of incident hypothyroidism for the shift work total group that included all shifts compared with the daytime work group was 1.27 (95% CI: 1.15-1.40). For the fixed evening, fixed night, rotating shift, and other shift workers, the multivariable-adjusted HRs (95% CI) were 1.11 (0.76-1.61), 2.18 (1.20-3.93), 1.39 (1.23-1.56), and 1.00 (0.82-1.22), respectively. In subgroup analyses by age, the association between shift work and hypothyroidism was more pronounced in younger participants (< 40 years; HR: 1.31; 95% CI: 1.16-1.47). Conclusions: Our large-scale cohort study showed an association between shift work and the incidence of hypothyroidism, especially in younger workers with night shifts.

Predicting amyloid PET positivity using plasma p-tau181 and other blood-based biomarkers.

Introduction: This study aimed to determine the efficacy of combining plasma phosphorylated tau (p-tau)181, amyloid beta (Aß)42/Aß40, neurofilament light (NfL), and apolipoprotein E (APOE) genotypes for detecting positive amyloid positron emission tomography (PET), which is little known in the Asian population, in two independent cohorts. Methods: Biomarkers were measured using a single-molecule array (Simoa) in a cohort study (Asan). All participants underwent amyloid PET. Significant changes in the area under the curve (AUC) and Akaike Information Criterion values were considered to determine the best model. The generalizability of this model was tested using another cohort (KBASE-V). Results: In the Asan cohort, after adjusting for age and sex, p-tau181 (AUC = 0.854) or APOE ε4 status (AUC = 0.769) distinguished Aß status with high accuracy. Combining them or adding NfL and Aß42/40 improved model fitness. The best-fit model included the plasma p-tau181, APOE ε4, NfL and Aß42/40. The models established from the Asan cohort were tested in the KBASE-V cohort. Additionally, in the KBASE-V cohort, these three biomarker models had similar AUC in cognitively unimpaired (AUC = 0.768) and mild cognitive impairment (MCI) (AUC = 0.997) participants. Conclusions: Plasma p-tau181 showed a high performance in determining Aß-PET positivity. Adding plasma NfL and APOE ε4 status improved the model fit without significant improvement in AUC.

Association between hearing loss and high-sensitivity C-reactive protein: the Kangbuk Samsung Cohort Study.

Background: Hearing loss (HL) is linked to an elevated risk of cardiovascular diseases (CVDs). The pathogeneses of HL and CVD commonly involve inflammatory responses. Previous studies investigated elevated levels of inflammatory biomarkers in subjects with HL, however, their findings did not demonstrate statistical significance. In our cross-sectional and longitudinal study, we investigated the correlation between HL and increased high-sensitivity C-reactive protein (hsCRP) levels to determine how HL is associated with CVDs. Methods: We conducted a cross-sectional study with workers aged over 18 years who underwent health check-ups at our institution between 2012 and 2018 (n = 566,507), followed by conducting a longitudinal study of workers aged > 18 who underwent health checkups at least twice at our institution between 2012 and 2018 (n = 173,794). The definition of HL was as an average threshold of ≥ 20 dB in pure-tone air conduction at 0.5, 1.0, and 2.0 kHz in both ears. The incidence of increased hsCRP levels throughout the follow-up period was defined as a level exceeding 3 mg/L. Logistic regression and generalized estimating equations were performed to estimate the risk of increased hsCRP levels according to the occurrence of HL in groups stratified by age. Results: In the cross-sectional study, the multivariate-adjusted odds ratio (OR) was 1.17 (95% confidence interval [CI]: 1.02-1.34); the OR was 0.99 (95% CI: 0.80-1.22) in those under 40 and 1.28 (1.08-1.53) in those over 40. In the longitudinal study, the multivariable-adjusted OR was 1.05 (95% CI: 0.92-1.19); the OR was 1.10 (95% CI: 0.90-1.35) in those under 40 and 1.20 (1.01-1.43) in those over 40. Conclusions: This cross-sectional and longitudinal study identified an association between HL and increased hsCRP levels in workers aged over 40 years.