Shorter total sleep time is associated with lower CD4+/CD8+ T cell ratios in virally suppressed men with HIV.

Study Objectives: Although poor sleep quality is associated with lower CD4+ T cell counts among people living with HIV (PLWH), the association between objective sleep metrics and T lymphocyte subset counts is unknown. We evaluated the association between polysomnography (PSG) derived sleep metrics and T lymphocyte subpopulations in a cohort of men living with HIV. Methods: Virally suppressed men living with HIV participating in the Multicenter AIDS Cohort Study underwent home overnight PSG. We assessed the association of PSG parameters with CD4+ and CD8+ T cell counts and the CD4+/CD8+ T cell ratio. Results: Overall, 289 men with mean (±SD) age 55.3 ±â€…11.3 years and mean CD4+ T cell count 730 ±â€…308 cells/mm3 were evaluated. Total sleep time (TST) was significantly associated with CD8+ but not CD4+ T cell counts. After adjusting for age, race, depressive symptoms, antidepressant use, and non-nucleoside reverse transcriptase inhibitors use, every hour of shorter TST was associated with an additional 33 circulating CD8+ T cells/mm3 (p = 0.05) and a 5.6% (p = 0.0007) decline in CD4+/CD8+ T cell ratio. In adjusted models, every hour of shorter rapid eye movement (REM) sleep was associated with an additional 113 CD8+ T cells/mm3 (p = 0.02) and a 15.1% lower CD4+/CD8+ T cell ratio (p = 0.006). In contrast, measures of sleep efficiency and sleep-disordered breathing were not associated with differences in T lymphocyte subpopulations. Conclusions: Our findings suggest that shorter TST and REM sleep durations are associated with differences in T lymphocyte subpopulations among men living with HIV. Addressing sleep may reflect a novel opportunity to improve immune function in PLWH.

Automated Detection of Apical Foreshortening in Echocardiography Using Statistical Shape Modelling.

OBJECTIVE: Automated detection of foreshortening, a common challenge in routine 2-D echocardiography, has the potential to improve quality of acquisitions and reduce the variability of left ventricular measurements. Acquiring and labelling the required training data is challenging due to the time-intensive and highly subjective nature of foreshortened apical views. We aimed to develop an automatic pipeline for the detection of foreshortening. To this end, we propose a method to generate synthetic apical-four-chamber (A4C) views with matching ground truth foreshortening labels. METHODS: A statistical shape model of the four chambers of the heart was used to synthesise idealised A4C views with varying degrees of foreshortening. Contours of the left ventricular endocardium were segmented in the images, and a partial least squares (PLS) model was trained to learn the morphological traits of foreshortening. The predictive capability of the learned synthetic features was evaluated on an independent set of manually labelled and automatically curated real echocardiographic A4C images. RESULTS: Acceptable classification accuracy for identification of foreshortened views in the testing set was achieved using logistic regression based on 11 PLS shape modes, with a sensitivity, specificity and area under the receiver operating characteristic curve of 0.84, 0.82 and 0.84, respectively. Both synthetic and real cohorts showed interpretable traits of foreshortening within the first two PLS shape modes, reflected as a shortening in the long-axis length and apical rounding. CONCLUSION: A contour shape model trained only on synthesized A4C views allowed accurate prediction of foreshortening in real echocardiographic images.

Visible Light-Induced Metal-Free Fluoroalkylations.

Fluoroalkylation is a crucial synthetic process that enables the modification of molecules with fluoroalkyl groups, which can enhance the properties of compounds and have potential applications in medicine and materials science. The utilization of visible light-induced, metal-free methods is of particular importance as it provides an environmentally friendly alternative to traditional methods and eliminates the potential risks associated with metal-catalyst toxicity. This Account describes our studies on visible light-induced, metal-free fluoroalkylation processes, which include the use of organic photocatalysts or EDA complexes. We have utilized organophotocatalysts such as Nile red, tri(9-anthryl)borane, and an indole-based tetracyclic complex, as well as catalyst-free EDA chemistry through photoactive halogen bond formation or an unconventional transient ternary complex formation with nucleophilic fluoroalkyl source. A variety of π-systems including arenes/heteroarenes, alkenes, and alkynes have been successfully fluoroalkylated under the developed reaction conditions.

Comparison of posterior vitreous detachment-related and glaucomatous optic disc hemorrhage.

This study compared the characteristics of posterior vitreous detachment (PVD)-related and glaucomatous optic disc hemorrhage (DH). Fundus photographs of eyes with PVD-related DH (PVD group) and glaucomatous DH (glaucoma group) were reviewed. The shape, type, layer, location (clock-hour sector), and DH/disc area (DH/DA) ratio of DH were investigated. In the PVD group, DH presented as a flame (60.9%), splinter (34.8%), and dot or blot (4.3%) shape. However, most of the glaucomatous DH revealed a splinter shape (92.3%), followed by a flame shape (7.7%, p < 0.001). In the PVD group, the most common type of DH was cup margin type (52.2%), whereas, in the glaucoma group it was disc rim type (53.8%, p = 0.003). Both PVD-related and glaucomatous DH were most commonly observed in the 7 o'clock sector. In the PVD group, DH was also found in the 2 and 5 o'clock sectors (p = 0.010). Mean DH/DA ratio in PVD group (0.15 ± 0.19) was greater than in glaucoma group (0.04 ± 0.04, p < 0.001). PVD-related DH showed a higher frequency of flame shape, cup margin type, nasal location, and greater area compared to the glaucomatous DH.

Prevalence and Predictors of Sleep-Disordered Breathing in Men Participating in the Multicenter AIDS Cohort Study.

BACKGROUND: Data on the prevalence of sleep-disordered breathing (SDB) in people with HIV are limited. Moreover, whether the associations between SDB and age or BMI differ by HIV status is unknown. RESEARCH QUESTION: Is SDB more prevalent in men with HIV than those without HIV, and do the predictors of SDB differ between the two groups? STUDY DESIGN AND METHODS: Home polysomnography was used in the Multicenter AIDS Cohort Study to assess SDB prevalence in men with (n = 466; 92% virologically suppressed) and without (n = 370) HIV. SDB was defined using the oxygen desaturation index (ODI) and the apnea-hypopnea index (AHI), using four definitions: ≥ 5 events/h based on an ODI with a 3% (ODI3) or 4% (ODI4) oxygen desaturation, or an AHI with a 3% oxygen desaturation or EEG arousal (AHI3a) or with a 4% oxygen desaturation (AHI4). RESULTS: SDB prevalence was similar in men with and without HIV using the ODI3 and AHI3a definitions. However, SDB prevalence was higher in men with than without HIV using the ODI4 (55.9% vs 47.8%; P = .04) and the AHI4 definitions (57.9% vs 50.4%; P = .06). Mild and moderate SDB were more common in men with than without HIV. Associations between SDB prevalence and age, race, and BMI were similar in men with and without HIV. Among men with HIV, viral load, CD4 cell count, and use of antiretroviral medications were not associated with SDB prevalence. INTERPRETATION: SDB prevalence was high overall but greater in men with than without HIV using the ODI4 threshold definition. Efforts to diagnose SDB are warranted in people with HIV, given that SDB is associated with daytime sleepiness and impaired quality of life.

Synergistic Renoprotective Effect of Melatonin and Zileuton by Inhibition of Ferroptosis via the AKT/mTOR/NRF2 Signaling in Kidney Injury and Fibrosis

According to recent evidence, ferroptosis is a major cell death mechanism in the pathogenesis of kidney injury and fibrosis.Despite the renoprotective effects of classical ferroptosis inhibitors, therapeutic approaches targeting kidney ferroptosis remain limited. In this study, we assessed the renoprotective effects of melatonin and zileuton as a novel therapeutic strategy against ferroptosis-mediated kidney injury and fibrosis. First, we identified RSL3-induced ferroptosis in renal tubular epithelial HK-2 and HKC-8 cells. Lipid peroxidation and cell death induced by RSL3 were synergistically mitigated by the combination of melatonin and zileuton. Combination treatment significantly downregulated the expression of ferroptosis-associated proteins, 4-HNE and HO-1, and upregulated the expression of GPX4. The expression levels of p-AKT and p-mTOR also increased, in addition to that of NRF2 in renal tubular epithelial cells. When melatonin (20 mg/kg) and zileuton (20 mg/kg) were administered to a unilateral ureteral obstruction (UUO) mouse model, the combination significantly reduced tubular injury and fibrosis by decreasing the expression of profibrotic markers, such as α-SMA and fibronectin. More importantly, the combination ameliorated the increase in 4-HNE levels and decreased GPX4 expression in UUO mice. Overall, the combination of melatonin and zileuton was found to effectively ameliorate ferroptosis-related kidney injury by upregulating the AKT/mTOR/ NRF2 signaling pathway, suggesting a promising therapeutic strategy for protection against ferroptosis-mediated kidney injury and fibrosis.

Exercise capacity and risk of incident atrial fibrillation in healthy adults

Background/Aims@#Atrial fibrillation (AF) is a common arrhythmia and is associated with cardiovascular morbidity and mortality. It is important to identify and control the modifiable risk factors of AF. We aimed to examine the association of exercise capacity with the risk of incident AF within 3 years in healthy subjects. @*Methods@#We evaluated asymptomatic adults who had undergone more than two consecutive health checkups. We included subjects who exhibited normal sinus rhythm on the first health examination and who developed AF on the second or subsequent health examinations. Subjects who underwent cardiopulmonary exercise testing within 3 years before the diagnosis of AF were examined. @*Results@#The study population in the analyses included 428 cases (mean age 58.4 ± 7.6 yr, male 95.6%). There were significant differences in maximal systolic blood pressure (SBP; case 169.4 ± 24.2 vs. control 173.9 ± 22.3 mmHg), peak VO2 (29.5 ± 5.4 vs. 30.4 ± 4.8 mL/kg per minute), and maximal metabolic equivalents (METs; 8.5 ± 1.6 vs. 8.7 ± 1.4) between the two groups. In the multivariable logistic models, adjusted odds ratios were 0.99 for maximal SBP (95% confidence interval [CI] 0.98–0.99), 0.97 for peak VO2 (95% CI 0.95–0.99), and 0.91 for maximal METs (95% CI 0.83–0.98). @*Conclusions@#We demonstrated that poorer exercise capacity was associated with the development of AF in a healthy population. A prospective, systematic trial is necessary to confirm that appropriate exercise training will be beneficial in preventing the development of AF in such patients.

Validation of a Novel Endoscopic Feature that Predicts Helicobacter pylori-negative Status: Does the Scratch Sign Reflect H. pylori Non-infection?

Background/Aims@#Identification of Helicobacter pylori infection status is necessary as H. pylori is associated with gastric malignancy. Recently, a red linear scrape-like appearance on the gastric mucosa, called the “scratch sign,” was reported to be associated with H. pylori-negative gastric mucosal status. Herein, we aimed to validate the association between the scratch sign and H. pylori infection status. @*Methods@#The data of patients who underwent screening endoscopy at Bundang Jesaeng General Hospital between March 2023 and April 2023 were reviewed. Patients were classified as having an H. pylori current infection or non-infection status based on the results of rapid urease tests. Patients who had undergone H. pylori eradication therapy were excluded. Endoscopic features of the gastric mucosa were assessed using the Kyoto classification of gastritis. @*Results@#The scratch sign appeared more frequently in patients with non-infection than in those with current infection status (32.7% vs. 10.6%, respectively; P<0.001). Multivariate analysis showed that only the presence of sticky mucus was significantly associated with the presence of the scratch sign. Patient without the scratch sign had a higher prevalence of open-type atrophy, intestinal metaplasia, enlarged folds, and diffuse redness, which reflected a higher Kyoto score. @*Conclusions@#Presence of the gastric mucosal scratch sign, a novel endoscopic marker, is indicative of H. pylori-negative status and appears to be inversely correlated with the presence of sticky mucus. In addition to the Kyoto classification of gastritis, detection of the scratch sign may facilitate identification of the H. pylori infection status.

Monitoring Posterior Cerebral Perfusion Changes With Dynamic Susceptibility Contrast-Enhanced Perfusion MRI After Anterior Revascularization Surgery in Pediatric Moyamoya Disease

Objective@#To determine whether dynamic susceptibility contrast-enhanced (DSC) perfusion magnetic resonance imaging (MRI) can be used to evaluate posterior cerebral circulation in pediatric patients with moyamoya disease (MMD) who underwent anterior revascularization. @*Materials and Methods@#This study retrospectively included 73 patients with MMD who underwent DSC perfusion MRI (age, 12.2 ± 6.1 years) between January 2016 and December 2020, owing to recent-onset clinical symptoms during the follow-up period after completion of anterior revascularization. DSC perfusion images were analyzed using a dedicated software package (NordicICE; Nordic NeuroLab) for the middle cerebral artery (MCA), posterior cerebral artery (PCA), and posterior border zone between the two regions (PCA-MCA). Patients were divided into two groups; the PCA stenosis group included 30 patients with newly confirmed PCA involvement, while the no PCA stenosis group included 43 patients without PCA involvement. The relationship between DSC perfusion parameters and PCA stenosis, as well as the performance of the parameters in discriminating between groups, were analyzed. @*Results@#In the PCA stenosis group, the mean follow-up duration was 5.3 years after anterior revascularization, and visual disturbances were a common symptom. Normalized cerebral blood volume was increased, and both the normalized time-topeak (nTTP) and mean transit time values were significantly delayed in the PCA stenosis group compared with those in the no PCA stenosis group in the PCA and PCA-MCA border zones. TTP PCA (odds ratio [OR] = 6.745; 95% confidence interval [CI] = 2.665–17.074; P < 0.001) and CBVPCA-MCA (OR = 1.567; 95% CI = 1.021–2.406; P = 0.040) were independently associated with PCA stenosis. TTPPCA showed the highest receiver operating characteristic curve area in discriminating for PCA stenosis (0.895; 95% CI = 0.803–0.986). @*Conclusion@#nTTP can be used to effectively diagnose PCA stenosis. Therefore, DSC perfusion MRI may be a valuable tool for monitoring PCA stenosis in patients with MMD.

Comparison of interdental brush size and label information marketed in Korea / 대한구강보건학회지

Objectives@#This study compares the labeling information on the sizes of interdental brushes marketed in Korea to their actual sizes. Moreover, it analyzes the relationship between the size of the passage hole diameter (PHD), brush diameter, stem diameter, and stem length. @*Methods@#Among the commercially available interdental brushes in Korea, 171 interdental brushes, 3 in each size, were collected from 9 companies. The labels of the collected interdental brushes were researched, and the PHD was measured and compared. The correlation between the passage hole diameter, brush diameter, stem diameter, and stem length was analyzed. Multiple regression analysis was performed to verify the effect of brush diameter, stem diameter, and stem length on the determination of the PHD. @*Results@#The sizes of the interdental brushes were expressed using the ISO labeling or the Small, Medium, Large (S, M, L) labeling and indicated in units of 0.1. The concordance rate of the measured PHD and named PHD was 39.7%. The measured brush diameter, stem diameter, and stem length increased as the interdental brush size increased. There was a significant correlation (P<0.01) between PHD, brush diameter, stem diameter, and stem length. The order of variables with the most to least significant influence on PHD was stem diameter (β=0.528), brush diameter (β=0.404), and stem length (β=0.074). @*Conclusions@#This study shows that the label and actual size of interdental brushes did not match, and the concordance rate between the measured and labeled PHDs was low. Therefore, the interdental brush size labels among manufacturers should be standardized. Moreover, these manufacturers must provide the correct size information for the interdental brushes.

Efficacy and Safety of Galcanezumab as a Preventive Treatment for Episodic Migraine in South Korean Patients: A Post-Hoc Analysis of a Phase 3 Clinical Trial

Background@#and Purpose The estimated prevalence of migraines in South Korea is 6.0%, with affected patients having unmet needs. The efficacy, safety, and tolerability of galcanezumab, a humanized monoclonal antibody, for episodic migraine (EM) prevention was evaluated in South Korean patients. @*Methods@#During the double-blind period of the EVOLVE-2 phase 3 trial, patients with EM were randomized into placebo, 120 mg-galcanezumab, and 240-mg galcanezumab treatment groups. The primary endpoint was the overall mean change from baseline in the number of monthly migraine headache days during the 6-month double-blind period. We conducted a post-hoc analysis of the South Korean cohort in EVOLVE-2. @*Results@#Among 98 South Korean patients in the intent-to-treat population, significant changes from baseline were observed in the number of monthly migraine headache days in the 240-mg galcanezumab group compared with the placebo group (-2.64, p=0.013), in the percentage of patients with ≥50% reduction in the number of monthly migraine headache days (120 mg: odds ratio=2.43, p=0.030; 240 mg: odds ratio=2.60, p=0.019), in the number of monthly migraine headache days with acute medication use (120 mg: -2.22, p=0.006; 240 mg: -2.23, p=0.005), and in the Migraine-Specific Quality-of-Life Role Function-Restrictive (120 mg: 8.34, p=0.040). Numerical improvements from baseline were observed relative to the placebo group in at least one galcanezumab group for: the percentage of patients with ≥75% reduction in the number of monthly migraine headache days functional impairment, and disease severity. The most common treatment-emergent adverse event in the combined galcanezumab group was injection site reaction, which led to treatment discontinuation for one patient. @*Conclusions@#Galcanezumab treatment demonstrated efficacy and a favorable safety and tolerability profile in South Korean patients with EM.

Development and Evaluation of Deep Learning-Based Automatic Segmentation Model for Skull Zero TE MRI in Children

Purpose@#To develop and evaluate a deep learning technique to automatically segment bone structures in zero echo time (ZTE) for skull magnetic resonance imaging (MRI) in children. @*Materials and Methods@#From January to December 2021, 38 bone ZTE MRIs from infants and children (age range, 1–31 months) were collected for model development.Mask images were generated by manually segmenting the craniofacial bone using a commercial segmentation program. Among them, 35 ZTE series were used to train the three-dimensional (3D)-nnUnet deep learning model and the remaining three series were used for model validation. A temporally different dataset of 19 ZTE bone MRIs obtained in May 2022 from infants and children (age range, 3–168 months) was used to determine the model’s performance. Dice similarity coefficient was calculated for each test case.From 3D volume rendering images, segmentation accuracy, overall image quality, and visibility of cranial sutures were subjectively evaluated on a 5-point scale and compared with ground truth data from manual segmentation. Reasons for segmentation failure were analyzed using axially segmented ZTE images. @*Results@#For the test set, the mean Dice similarity coefficient was 0.985 ± 0.019. The segmentation accuracy was lower than the ground truth without showing a statistically significant difference between the two (3.39 ± 1.11 vs. 3.73 ± 0.77, p = 0.055). The overall image quality and suture visibility showed no significant difference (3.34 ± 0.75 vs.3.42 ± 0.69, p = 0.317; 3.55 ± 0.97 vs. 3.60 ± 0.95, p = 0.157). Common reasons for low segmentation accuracy were well-pneumatized sinuses, metal artifacts, skin at the vertex level, and bones too thin. @*Conclusion@#The deep learning-based automatic segmentation technique of bone ZTE MRIs showed comparable segmentation performance to manual segmentation. Using the deep learning-based segmentation results, acceptable 3D-volume rendering images of craniofacial bones were generated.

Cerebrovascular Arteriopathy in Microcephalic Osteodysplastic Primordial Dwarfism Type II

Microcephalic osteodysplastic primordial dwarfism type II (MOPD-II) is a rare disease with characteristic skeletal abnormalities and severe comorbidities related to cerebrovascular diseases. It is frequently associated with early onset cerebrovascular diseases due to its predisposition to intracranial arteriopathies such as aneurysms and moyamoya syndrome. Herein, we report cases of two siblings presenting with multiple cerebral aneurysms and moyamoya syndrome. Two brothers with short stature were genetically diagnosed with MOPD-II at the age of 18 years and 9 years. Magnetic resonance angiography of the brother at the age of 20 years demonstrated a ruptured left A2 aneurysm with multiple variable-sized aneurysms in intracerebral arteries. The younger brother underwent brain imaging for screening at the age of 12 years which revealed a sizable basilar top aneurysm, multiple tiny aneurysms, and steno-occlusive changes in the left A1 and M1. In conclusion, cerebrovascular arteriopathy was diagnosed using brain magnetic resonance imaging in a pediatric patient with MOPD-II. Cerebrovascular comorbidities can occur at any point in life. It can lead to disability or death. Therefore, routine screening for cerebrovascular comorbidities in patients with MOPD-II who have reached adolescence is recommended.

Comparison of Ocular Biometric Measurements Using New Swept-source Optical-coherence Tomography, Low-coherence Reflectometry, A-Scan Biometry, and Autokeratometry

Purpose@#We compared optical biometric measurements made using new swept-source optical-coherence tomography, low-coherence reflectometry, autokeratometry, and A-scan biometry. @*Methods@#In total, 86 eyes of 47 patients were included. Axial length, lens thickness, central corneal thickness, anterior chamber depth, and corneal curvature were measured using the Anterion® (Heidelberg Engineering, inc., Heidelberg, Germany) and Lenstar LS 900® (Haag-Streit AG, Koeniz, Switzerland) platforms. Corneal curvature and axial length were measured using the Essilor AKR 750® (Essilor instruments, France, Charenton-le-Pont) and PacScan 300A® (Sonomed Inc., Chicago, IL, USA) platforms, respectively. The evaluated biometric parameters were compared and verified; intraclass correlation coefficients and Bland-Altman plots were used to analyze statistical agreement. @*Results@#The differences between the Anterion® and Lenstar LS 900® platforms in terms of axial length, lens thickness, central corneal thickness, anterior chamber depth, and white-to-white diameter were -0.02 ± 0.08, 0.08 ± 0.13, -2.66 ± 11.12, 0.05 ± 0.12, and 0.08 ± 0.26, respectively. All values were statistically significant. The mean corneal curvature between Anterion® and Lenstar LS 900® had a statistically significant difference of -0.08 ± 0.47, while the difference between the Anterion® and AKR 750® platforms was not significant. Biometric parameters measured using an Anterion® and other devices showed a strong positive correlation when assessed using Pearson’s correlation analysis; there was good agreement between the results when analyzed using intraclass correlation coefficients and Bland-Altman plots. @*Conclusions@#Optical biometric measurements made using the Anterion® platform were not significantly different from those obtained using other devices, but there were significant differences compared to the Lenstar LS 900® platform. Since these significant differences could influence decision making during intraocular lens selection for cataract surgery, the values are clinically useful for reference.

Safety and Efficacy of Intravenous Thrombolysis in the 3- to 4.5-hour Window in Acute Ischemic Stroke Patients Who Have Both Diabetes Mellitus and History of Prior Stroke

Background@#For acute ischemic stroke (AIS) patients with history of prior stroke (PS) and diabetes mellitus (DM), intravenous recombinant tissue plasminogen activator (IV-tPA) therapy in the 3- to 4.5-hour window is off-label in Korea. This study aimed to assess the safety and efficacy of IV-tPA in these patients. @*Methods@#Using data from a prospective multicenter stroke registry between January 2009 and March 2021, we identified AIS patients who received IV-tPA in the 3- to 4.5-hour window, and compared the outcomes of symptomatic intracranial hemorrhage (SICH), 3-month mortality, 3-month modified Rankin Scale (mRS) score 0-1 and 3-month mRS distribution between patients with both PS and DM (PS/DM, n=56) versus those with neither PS nor DM, or with only one (non-PS/DM, n=927). @*Results@#The PS/DM group versus the non-PS/DM group was more likely to have a prior disability, hypertension, hyperlipidemia, coronary heart disease and less likely to have atrial fibrillation. The PS/DM and the non-PS/DM groups had comparable rates of SICH (0% vs. 1.7%; p>0.999) and 3-month mortality (10.7% vs. 10.2%; p=0.9112). The rate of 3-month mRS 0-1 was non-significantly lower in the PS/DM group than in the non-PS/DM group (30.4% vs. 40.7%; adjusted odds ratio [95% confidence interval], 0.81 [0.41-1.59]). @*Conclusions@#In the 3- to 4.5-hour window, AIS patients with PS/DM, as compared to those with non-PS/DM, might benefit less from IV-tPA. However, given the similar risks of SICH and mortality, IV-tPA in the late time window could be considered in patients with both PS and DM.

Comprehensive Molecular Characterization of Soft Tissue Sarcoma for Prediction of Pazopanib-Based Treatment Response / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Even though pazopanib, a multitargeted tyrosine kinase inhibitor, has been approved for refractory soft tissue sarcoma (STS), little is known about the molecular determinants of the response to pazopanib. We performed integrative molecular characterization to identify potential predictors of pazopanib efficacy. @*Materials and Methods@#We obtained fresh pre-treatment tumor tissue from 35 patients with advanced STS receiving pazopanib-based treatment. Among those, 18 (51.4%) received pazopanib monotherapy, and the remaining 17 (48.6%) received pazopanib in combination with durvalumab, programmed death-ligand 1 blockade. Whole-exome and transcriptome sequencing were performed for each tumor and patient germline DNA. @*Results@#Of the 35 patients receiving pazopanib-based treatment, nine achieved a partial response (PR), resulting in an objective response rate (ORR) of 27.3%, and the median progression-free survival (PFS) was 6.0 months. Patients with CDK4 amplification (copy ratio tumor to normal > 2) exhibited shorter PFS (3.7 vs. 7.9 months, p=2.09×10–4) and a poorer response (ORR; 0% vs. 33.3%) compared to those without a gene amplification (copy ratio ≤ 2). Moreover, non-responders demonstrated transcriptional activation of CDK4 via DNA amplification, resulting in cell cycle activation. In the durvalumab combination cohort, seven of the 17 patients (41.2%) achieved a PR, and gene expression analysis revealed that durvalumab responders exhibited high immune/stromal cell infiltration, mainly comprising natural killer cells, compared to non-responders as well as increased expression of CD19, a B-cell marker. @*Conclusion@#Despite the limitation of heterogeneity in the study population and treatment, we identified possible molecular predictors of pazopanib efficacy that can be employed in future clinical trials aimed at evaluating therapeutic strategies.

Usefulness of two-dimensional shear wave elastography in diagnosing hepatic veno-occlusive disease in pediatric patients undergoing hematopoietic stem cell transplantation

Purpose@#This study aimed to evaluate the usefulness of two-dimensional shear wave elastography (2D-SWE) in diagnosing hepatic veno-occlusive disease (VOD) in pediatric patients. @*Methods@#This study retrospectively included pediatric patients who underwent hematopoietic stem cell transplantation (HSCT) between November 2019 and January 2021. All 34 patients (8.7±5.0 years) were examined using 2D-SWE for an initial diagnosis. A subgroup analysis was performed using the data from follow-up examinations of patients diagnosed with VOD. The characteristics of the initial VOD diagnosis were compared with the longitudinal changes observed in VOD patients who underwent multiple ultrasound examinations. @*Results@#In total, 19 patients were diagnosed with VOD at 17.6±9.4 days after HSCT. All VOD patients showed hepatomegaly, ascites, and gallbladder wall thickening. Liver stiffness was higher in VOD patients than in non-VOD patients (12.4±1.1 vs. 6.3±0.8 kPa, P<0.001). Liver stiffness values above 7.2 kPa showed 84.2% sensitivity and 93.3% specificity in distinguishing VOD from non-VOD (area under the curve, 0.925; 95% confidence interval, 0.780 to 0.987; P<0.001). A subgroup analysis of 11 patients showed a linear decrease in liver stiffness values after VOD diagnosis with treatment (first, second, and third follow-ups; 13.5±1.7, 11.3±1.4, and 9.5±0.8 kPa, respectively), but without statistical significance in the pairwise analysis. @*Conclusion@#Liver stiffness measured using 2D-SWE increased in pediatric patients who develop VOD after HSCT. Therefore, liver stiffness can be a predictive and quantitative parameter for diagnosing VOD.

Ultrasound findings of subpial hemorrhage in neonates

Purpose@#Subpial hemorrhage (SPH) is a subtype of intracranial hemorrhage characterized by damage to the adjacent brain parenchyma. The aim of this study was to describe the sonographic features of SPH in neonates. @*Methods@#The cranial ultrasound (US) findings of neonates with SPH confirmed by brain magnetic resonance imaging (MRI) were analyzed retrospectively. Initial and follow-up US and MRI scans were reviewed by two pediatric radiologists who were blinded to both clinical history and outcomes. The US features were compared with the MRI findings. @*Results@#Sixteen patients were included (median gestational age, 38 weeks; range, 26 to 40 weeks; 69% term). SPH was detected most often in the temporal lobe (63%), and multiple SPHs were found in seven of 16 neonates, based on MRI. Acute SPH with an underlying venous infarct (UVI) was detected on US in 15 of 16 patients: small or large fan-shaped hyperechoic lesions (n=7 and 4, respectively) and gyriform hyperechoic lesions (n=4). The sonographic yin-yang sign was observed in three of the four large fan-shaped SPH cases. The accompanying findings on US were intraventricular hemorrhage (four out of six MRI-confirmed cases), and concurrent periventricular venous infarcts (five out of nine MRI-confirmed cases). In five patients, subpial cysts were observed on follow-up US or MRI (n=4 and n=4, respectively). @*Conclusion@#Acute SPH with UVI can appear as a peripheral fan-shaped or gyriform hyperechoic lesion on cranial US. SPH can be detected and suspected based on the US features of SPH with the accompanying findings.

Combinatorial Effect of Mesenchymal Stem Cells and Extracellular Vesicles in a Hydrogel on Cartilage Regeneration

BACKGROUND@#Mesenchymal stem cells (MSCs) are used for tissue regeneration due to their wide differentiation capacity and anti-inflammatory effects. Extracellular vesicles (EVs) derived from MSCs are also known for their regenerative effects as they contain nucleic acids, proteins, lipids, and cytokines similar to those of parental cells. There are several studies on the use of MSCs or EVs for tissue regeneration. However, the combinatorial effect of human MSCs (hMSCs) and EVs is not clear. In this study, we investigated the combinatorial effect of hMSCs and EVs on cartilage regeneration via co-encapsulation in a hyaluronic-acid (HA)-based hydrogel. @*METHODS@#A methacrylic-acid-based HA hydrogel was prepared to encapsulate hMSCs and EVs in hydrogels. Through in vitro and in vivo analyses, we investigated the chondrogenic potential of the HA hydrogel-encapsulated with hMSCs and EVs. @*RESULTS@#Co-encapsulation of hMSCs with EVs in the HA hydrogel increased the chondrogenic differentiation of hMSCs and regeneration of damaged cartilage tissue compared with that of the HA hydrogel loaded with hMSCs only. @*CONCLUSION@#Co-encapsulation of hMSCs and EVs in the HA hydrogel effectively enhances cartilage tissue regeneration due to the combinatorial therapeutic effect of hMSCs and EVs. Thus, in addition to cartilage tissue regeneration for the treatment of osteoarthritis, this approach would be a useful strategy to improve other types of tissue regeneration.

Deep Learning-Based Computed Tomography Image Standardization to Improve Generalizability of Deep Learning-Based Hepatic Segmentation

Objective@#We aimed to investigate whether image standardization using deep learning-based computed tomography (CT) image conversion would improve the performance of deep learning-based automated hepatic segmentation across various reconstruction methods. @*Materials and Methods@#We collected contrast-enhanced dual-energy CT of the abdomen that was obtained using various reconstruction methods, including filtered back projection, iterative reconstruction, optimum contrast, and monoenergetic images with 40, 60, and 80 keV. A deep learning based image conversion algorithm was developed to standardize the CT images using 142 CT examinations (128 for training and 14 for tuning). A separate set of 43 CT examinations from 42 patients (mean age, 10.1 years) was used as the test data. A commercial software program (MEDIP PRO v2.0.0.0, MEDICALIP Co. Ltd.) based on 2D U-NET was used to create liver segmentation masks with liver volume. The original 80 keV images were used as the ground truth. We used the paired t-test to compare the segmentation performance in the Dice similarity coefficient (DSC) and difference ratio of the liver volume relative to the ground truth volume before and after image standardization. The concordance correlation coefficient (CCC) was used to assess the agreement between the segmented liver volume and ground-truth volume. @*Results@#The original CT images showed variable and poor segmentation performances. The standardized images achieved significantly higher DSCs for liver segmentation than the original images (DSC [original, 5.40%–91.27%] vs. [standardized, 93.16%–96.74%], all P < 0.001). The difference ratio of liver volume also decreased significantly after image conversion (original, 9.84%–91.37% vs. standardized, 1.99%–4.41%). In all protocols, CCCs improved after image conversion (original, -0.006–0.964 vs. standardized, 0.990–0.998). @*Conclusion@#Deep learning-based CT image standardization can improve the performance of automated hepatic segmentation using CT images reconstructed using various methods. Deep learning-based CT image conversion may have the potential to improve the generalizability of the segmentation network.