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.

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.

Outcomes of not using tracheoplasty in asymptomatic tracheal stenosis found during open-heart surgery.

OBJECTIVES: We aimed to review the outcomes of treating incidentally encountered asymptomatic airway stenosis during open-heart surgery conservatively without the use of tracheoplasty. METHODS: Between January 2002 and October 2022, 25 patients were incidentally diagnosed with tracheal stenosis during open-heart surgery. Intraoperative bronchoscopy and/or laryngoscopy revealed tracheal stenosis; however, this was not consistent with the findings of the preoperative computed tomography. Patients who were diagnosed with a pulmonary artery or vascular sling or had moderate-to-severe respiratory symptoms before open-heart surgery were excluded. RESULTS: The median age and weight of the patients at operation were 3.0 months and 5.1 kg, respectively. They were categorized as those having tracheal stenosis on preoperative computed tomography (n = 12) or not having tracheal stenosis (n = 13). The narrowest diameter was significantly smaller in the former group (3.0 vs 5.8 mm, P < 0.05). The rates of reintubation and the tracheostomy, and intubation days tended to be higher in former group without statistical significance. Stenotic degree improved 2 months and 1 year or more after the operation (39.3% at operation, 28.4% at 2 months, 12.5% after 1 year). All patients were Ross class 1 or 2 at follow-up (mean, 7.1 years). CONCLUSIONS: Patients with tracheal stenosis showed tolerable long-term outcomes without using tracheoplasty. Accordingly, if tracheal stenosis, that would cause intubation difficulty, was incidentally revealed, concomitant tracheoplasty may not be required during open-heart surgery if the stenosis did not cause considerable symptoms or signs preoperatively.

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).

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.

Right lower lung midline herniation as a rare complication in an infant with heart-lung transplantation: A case report.

BACKGROUND: Lung herniation is a rare complication of heart-lung transplantation that can be fatal owing to vascular compromise and airway obstruction. To date, only five cases of lung herniation related to heart-lung transplantation have been reported in the literature; however, to the best of our knowledge, this is the first worldwide report of heart-lung transplantation-related lung herniation in an infant. METHODS: We describe the case of lung herniation as a rare heart-lung transplantation-related complication in an infant. A 12-month-old female baby developed severe bronchopulmonary dysplasia with severe pulmonary hypertension, and she underwent extracorporeal membrane oxygenation for cardiac collapse and lung support. Then, we performed heart-lung transplantation to manage the irreversible deterioration of her lung function. After the heart-lung transplantation, we found the radiological abnormalities persisted on follow-up chest radiographs until the 13th postoperative day diagnosed as lung herniation of the right lower lobe on chest computed tomography. RESULTS: After the relocation of the herniated lung, the clinical condition of the patient improved, and the patient is currently growing without any respiratory symptoms. CONCLUSIONS: In this case report, we emphasize that clinical awareness and high suspicion of this rare complication are needed for early diagnosis and proper treatment to prevent post-transplantation morbidity and mortality related to potential ischemic injury.

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.

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.

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.].

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.

Extubation in operating room versus early extubation in ICU after open-heart surgery in patients with CHDs.

BACKGROUNDS AND OBJECTIVES: The "Fast track" protocol is an early extubation strategy to reduce ventilator-associated complications and induce early recovery after open-heart surgery. This study compared clinical outcomes between operating room extubation and ICU extubation after open-heart surgery in patients with CHD. METHODS: We retrospectively reviewed 215 patients who underwent open-heart surgery for CHDs under the scheduled "Fast track" protocol between September 2016 and April 2022. The clinical endpoints were post-operative complications, including bleeding, respiratory and neurological complications, and hospital/ICU stays. RESULTS: The patients were divided into operating room extubation (group O, n = 124) and ICU extubation (group I, n=91) groups. The most frequently performed procedures were patch closures of the atrial septal (107/215, 49.8%) and ventricular septal (89/215, 41.4%) defects. There were no significant differences in major post-operative complications or ICU and hospital stay duration between the two groups; however, patients in group I showed longer mechanical ventilatory support (0.0 min vs. 59.0 min (interquartile range: 17.0-169.0), p < 0.001). Patients in Group O showed higher initial lactate levels (3.2 ± 1.7 mg/dL versus 2.5 ± 2.0 mg/dL, p = 0.007) and more frequently used additional sedatives and opioid analgesics (33.1% versus 19.8%, p = 0.031). CONCLUSIONS: Extubation in the operating room was not beneficial for patients during post-operative ICU or hospital stay. Early extubation in the ICU resulted in more stable hemodynamics in the immediate post-operative period and required less use of sedatives and analgesics.

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.

Etiology of White Matter Hyperintensities in Autosomal Dominant and Sporadic Alzheimer Disease.

Importance: Increased white matter hyperintensity (WMH) volume is a common magnetic resonance imaging (MRI) finding in both autosomal dominant Alzheimer disease (ADAD) and late-onset Alzheimer disease (LOAD), but it remains unclear whether increased WMH along the AD continuum is reflective of AD-intrinsic processes or secondary to elevated systemic vascular risk factors. Objective: To estimate the associations of neurodegeneration and parenchymal and vessel amyloidosis with WMH accumulation and investigate whether systemic vascular risk is associated with WMH beyond these AD-intrinsic processes. Design, Setting, and Participants: This cohort study used data from 3 longitudinal cohort studies conducted in tertiary and community-based medical centers-the Dominantly Inherited Alzheimer Network (DIAN; February 2010 to March 2020), the Alzheimer's Disease Neuroimaging Initiative (ADNI; July 2007 to September 2021), and the Harvard Aging Brain Study (HABS; September 2010 to December 2019). Main Outcome and Measures: The main outcomes were the independent associations of neurodegeneration (decreases in gray matter volume), parenchymal amyloidosis (assessed by amyloid positron emission tomography), and vessel amyloidosis (evidenced by cerebral microbleeds [CMBs]) with cross-sectional and longitudinal WMH. Results: Data from 3960 MRI sessions among 1141 participants were included: 252 pathogenic variant carriers from DIAN (mean [SD] age, 38.4 [11.2] years; 137 [54%] female), 571 older adults from ADNI (mean [SD] age, 72.8 [7.3] years; 274 [48%] female), and 318 older adults from HABS (mean [SD] age, 72.4 [7.6] years; 194 [61%] female). Longitudinal increases in WMH volume were greater in individuals with CMBs compared with those without (DIAN: t = 3.2 [P = .001]; ADNI: t = 2.7 [P = .008]), associated with longitudinal decreases in gray matter volume (DIAN: t = -3.1 [P = .002]; ADNI: t = -5.6 [P < .001]; HABS: t = -2.2 [P = .03]), greater in older individuals (DIAN: t = 6.8 [P < .001]; ADNI: t = 9.1 [P < .001]; HABS: t = 5.4 [P < .001]), and not associated with systemic vascular risk (DIAN: t = 0.7 [P = .40]; ADNI: t = 0.6 [P = .50]; HABS: t = 1.8 [P = .06]) in individuals with ADAD and LOAD after accounting for age, gray matter volume, CMB presence, and amyloid burden. In older adults without CMBs at baseline, greater WMH volume was associated with CMB development during longitudinal follow-up (Cox proportional hazards regression model hazard ratio, 2.63; 95% CI, 1.72-4.03; P < .001). Conclusions and Relevance: The findings suggest that increased WMH volume in AD is associated with neurodegeneration and parenchymal and vessel amyloidosis but not with elevated systemic vascular risk. Additionally, increased WMH volume may represent an early sign of vessel amyloidosis preceding the emergence of CMBs.

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

Background and purpose: To develop and validate a deep learning-based automatic segmentation model for assessing intracranial volume (ICV) and to compare the accuracy determined by NeuroQuant (NQ), FreeSurfer (FS), and SynthSeg. Materials and methods: This retrospective study included 60 subjects [30 Alzheimer's disease (AD), 21 mild cognitive impairment (MCI), 9 cognitively normal (CN)] from a single tertiary hospital for the training and validation group (50:10). The test group included 40 subjects (20 AD, 10 MCI, 10 CN) from the ADNI dataset. We propose a robust ICV segmentation model based on the foundational 2D UNet architecture trained with four types of input images (both single and multimodality using scaled or unscaled T1-weighted and T2-FLAIR MR images). To compare with our model, NQ, FS, and SynthSeg were also utilized in the test group. We evaluated the model performance by measuring the Dice similarity coefficient (DSC) and average volume difference. Results: The single-modality model trained with scaled T1-weighted images showed excellent performance with a DSC of 0.989 ± 0.002 and an average volume difference of 0.46% ± 0.38%. Our multimodality model trained with both unscaled T1-weighted and T2-FLAIR images showed similar performance with a DSC of 0.988 ± 0.002 and an average volume difference of 0.47% ± 0.35%. The overall average volume difference with our model showed relatively higher accuracy than NQ (2.15% ± 1.72%), FS (3.69% ± 2.93%), and SynthSeg (1.88% ± 1.18%). Furthermore, our model outperformed the three others in each subgroup of patients with AD, MCI, and CN subjects. Conclusion: Our deep learning-based automatic ICV segmentation model showed excellent performance for the automatic evaluation of ICV.

Valve-Sparing Neo-Aortic Root Replacement for Neo-Aortic Root Dilatation 20 Years after Arterial Switch Operation for Transposition of the Great Arteries: A Case Report.

A 25-year-old man returned to Seoul National University Children's Hospital with mild dyspnea on exertion. He had undergone an arterial switch operation at 1 month after birth to correct a complete transposition of the great arteries and a ventricular septal defect. When the patient was 15 years old, dilatation of the neo-aortic sinus and annulus was first identified; since then, it had gradually increased. Given the young age of the patient and the degree of aortic regurgitation (AR), which was mild to moderate, we opted to perform a valve-sparing neo-aortic root replacement with aortic valve repair. Postoperative echocardiography showed successful reductions in the sizes of the aortic sinus and annulus, with only mild AR remaining.

Detection rate of contrast-enhanced brain magnetic resonance imaging in patients with cognitive impairment.

INTRODUCTION: The number of brain MRI with contrast media performed in patients with cognitive impairment has increased without universal agreement. We aimed to evaluate the detection rate of contrast-enhanced brain MRI in patients with cognitive impairment. MATERIALS AND METHODS: This single-institution, retrospective study included 4,838 patients who attended outpatient clinics for cognitive impairment evaluation and underwent brain MRI with or without contrast enhancement from December 2015 to February 2020. Patients who tested positive for cognitive impairment were followed-up to confirm whether the result was true-positive and provide follow-up management. Detection rate was defined as the proportion of patients with true-positive results and was compared between groups with and without contrast enhancement. Individual matching in a 1:2 ratio according to age, sex, and year of test was performed. RESULTS: The overall detection rates of brain MRI with and without contrast media were 4.7% (57/1,203; 95% CI: 3.6%-6.1%) and 1.8% (65/3,635; 95% CI: 1.4%-2.3%), respectively (P<0.001); individual matching demonstrated similar results (4.7% and 1.9%). Among 1,203 patients with contrast media, 3.6% was only detectable with the aid of contrast media. The proportion of patients who underwent follow-up imaging or treatment for the detected lesions were significantly higher in the group with contrast media (2.0% and 0.6%, P < .001). CONCLUSIONS: Detection rate of brain MRI for lesions only detectable with contrast media in patients with cognitive impairment was not high enough and further study is needed to identify whom would truly benefit with contrast media.