Efficacy of Venetoclax and Azacitidine in Acute Myeloid Leukemia Compared to Azacitidine Monotherapy: Real-World Experience.

BACKGROUND/AIM: The combination of venetoclax (VEN) and azacitidine (AZA) (VEN+AZA) leads to higher complete remission rates and longer overall survival (OS) in patients with untreated acute myeloid leukemia (AML) who are ineligible for intensive combination chemotherapy. In practice, the doses of VEN and AZA are reduced at the attending physician's discretion to avoid adverse events; however, the impact of dose and duration reductions has not been fully clarified. We analyzed whether the efficacy was maintained with reduced VEN+AZA compared to AZA monotherapy in the real world. PATIENTS AND METHODS: A total of 33 patients were included; 17 (10 newly diagnosed, 7 primary refractory or relapsed) received VEN+AZA, and 16 (7 newly diagnosed, 9 primary refractory or relapsed) received AZA. We analyzed complete remission (CR) and CR with incomplete hematologic recovery (CRi) rates, OS, and the incidence of adverse events. RESULTS: CR/CRi were achieved in 7/17 (41.2%) and 11/17 (64.7%) patients in the VEN+AZA group and 0/15 (0%) and 2/15 (6.7%) patients in the AZA group, respectively. The CR/CRi rate was higher in the VEN+AZA group than in the AZA group (p=0.001). OS was longer in the VEN+AZA group than in the AZA group (p=0.03), with a median of 506 days [95% confidence interval (CI)=234-585 days] and 208 days (95% CI=52-343 days), respectively. CONCLUSION: The doses of the VEN+AZA combination were reduced at the attending physician's discretion, resulting in a higher CR/CRi rate and longer OS than AZA monotherapy and is considered useful for AML in the real world.

Effect of Luseogliflozin on Myocardial Flow Reserve in Patients with Type 2 Diabetes Mellitus (LUCENT-J Study).

INTRODUCTION: In patients with type 2 diabetes (T2D), treatment with sodium-glucose cotransporter-2 (SGLT2) inhibitors has been shown to reduce hospital admission rates for heart failure (HF). However, the multiple mechanisms hypothesized and investigated to explain the cardioprotection of SGLT2 inhibitors are not fully understood. OBJECTIVES: The effect of luseogliflozin on myocardial flow reserve (MFR) in patients with T2D (LUCENT-J) study aims to examine the effects of SGLT2 inhibitors on myocardial perfusion. METHODS: The LUCENT-J study is a prospective, single-center, randomized, two-arm, parallel-group, open-label (i.e., the radiology readers are blinded), active-controlled study. A cohort of 40 patients with T2D with no or stable (with no history of myocardial infarction and with or without previous percutaneous coronary intervention) coronary artery disease will be included. Patients will be randomized in a 1:1 ratio to luseogliflozin or control and treated for 24 weeks. The primary outcome is the change in MFR, as measured by 13N-ammonia positron emission tomography/computed tomography, from baseline to 24 weeks after treatment initiation. PLANNED OUTCOMES: The LUCENT-J study will elucidate the mechanisms of cardioprotection by SGLT2 inhibitors in patients with T2D. TRIAL REGISTRATION: Japan Registry of Clinical Trials (JRCTs051220016).

Stronger positive correlation of the left ventricular mass index and extracellular volume fraction with diastolic function in diabetic patients without myocardial infarction.

BACKGROUND: The structural and functional characteristics of the heart in patients with diabetes mellitus (DM) and without myocardial infarction (MI) are not fully understood. METHODS: We retrospectively analysed the data of patients with left ventricular ejection fraction (LVEF) ≥ 40% who underwent contrast-enhanced cardiac magnetic resonance imaging (CMR), which was also used to exclude MI, at two hospitals. Volumetric data and extracellular volume fraction (ECVf) of the myocardium evaluated using CMR were compared between patients with and without DM, and their association with diastolic function was evaluated. RESULTS: Among 322 analysed patients, 53 had DM. CMR revealed that the left ventricular mass index (LVMi) and ECVf were increased while LVEF was decreased in patients with DM after adjusting for patient characteristics (all P < 0.05). A stronger positive correlation was observed between LVMi and the early diastolic transmitral flow velocity to early diastolic mitral annular velocity ratio (E/e') in patients with DM than in those without DM (correlation coefficient [R] = 0.46, p = 0.001; R = 0.15, p = 0.021, respectively; p for interaction = 0.011). ECVf correlated with E/e' only in patients with DM (R = 0.61, p = 0.004). CONCLUSIONS: Patients with DM have increased LVMi and ECVf. Importantly, there was a difference between patients with and without DM in the relationship between these structural changes and E/e', with a stronger relationship in patients with DM. Furthermore, DM is associated with mildly reduced LVEF even in the absence of MI.

Side branch embolization before endovascular abdominal aortic aneurysm repair to prevent type II endoleak: A prospective multicenter study.

PURPOSE: The purpose of the study was to evaluate the efficacy and safety of pre-emptive transcatheter arterial embolization (P-TAE) of aortic side branches to prevent type II endoleak in patients with abdominal aortic aneurysm after endovascular abdominal aneurysm repair (EVAR). MATERIALS AND METHODS: This multicenter, prospective, single-arm trial enrolled 100 patients with abdominal aortic aneurysm from nine hospitals between 2018 and 2021. There were 85 men and 15 women, with a mean age of 79.6 ± 6.0 (standard deviation) years (range: 65-97 years). P-TAE was attempted for patent aortic side branches, including the inferior mesenteric artery, lumbar arteries, and other branches. The primary endpoint was late type II endoleak incidence at 6 months post-repair. Secondary endpoints included changes in aneurysmal sac diameter at 6- and 12 months, complications, re-intervention, and aneurysm-related mortality. Aneurysm sac changes at 6- and 12 months was compared between the late and no-late type II endoleak groups. RESULTS: Coil embolization was successful in 80.9% (321/397) of patent aortic side branches, including 86.3% of the inferior mesenteric arteries, 80.3% of lumbar arteries, and 55.6% of other branches without severe adverse events. Late type II endoleak incidence at 6 months was 8.9% (8/90; 95% confidence interval: 3.9-16.8%). Aneurysm sac shrinkage > 5 mm was observed in 41.1% (37/90) and 55.3% (47/85) of the patients at 6- and 12-months post-EVAR, respectively. Patients with late type II endoleak had less aneurysm sac shrinkage than those without type II endoleak at 12 months (-0.2 mm vs. -6.0 mm; P = 0.040). No patients required re-intervention for type II endoleak, and no aneurysm-related mortalities occurred. CONCLUSION: P-TAE is safe and effective in preventing type II endoleak, leading to early sac shrinkage at 12 months following EVAR.

Pre-emptive Aortic Side Branch Embolization during Endovascular Aneurysm Repair Using the Excluder Stent-Graft System: A Prospective Multicenter study.

PURPOSE: To evaluate the effectiveness and safety of pre-emptive transcatheter arterial embolization (P-TAE) for aortic side branches (ASBs) to prevent Type 2 endoleaks (EL2) before endovascular aneurysm repair (EVAR) using the Excluder stent-graft system (Excluder). MATERIALS AND METHODS: In this prospective, multicenter study, 80 patients (mean age, 79.1 years [SD ± 6.7]; 85.0% were men; mean aneurysmal sac diameter, 48.4 mm [SD ± 7.4]) meeting the eligibility criteria were prospectively enrolled from 9 hospitals. Before EVAR, P-TAE was performed to embolize the patent ASBs originating from the abdominal aortic aneurysm. Contrast-enhanced computed tomography (CT) was performed at 1 month and 6 months after EVAR. The primary endpoint was EL2 incidence at 6 months, and the secondary endpoints were aneurysmal sac diameter changes at 6 and 12 months, P-TAE outcomes, adverse events related to P-TAE, reintervention, and aneurysm-related mortality. RESULTS: All patients successfully underwent P-TAE without serious. Coil embolization was successful in 81.6% of ASBs. EL2 incidence at 6 months was identified in 18 of 70 (25.7%) patients. Aneurysmal sac diameter shrinkage (≥5 mm) was observed in 30.0% of patients at 6 months and in 40.9% at 12 months. Only 1 patient required reintervention for EL2 within 1 year of EVAR; aneurysm-related deaths were not observed. CONCLUSIONS: P-TAE for ASBs before EVAR using Excluder is a safe and effective strategy. It aids in achieving early aneurysmal sac shrinkage and reduces EL2 reintervention at 1 year after EVAR.

Covering the intercostal artery branching of the Adamkiewicz artery during endovascular aortic repair increases the risk of spinal cord ischemia.

Objectives: This study aimed to determine the relationship between covering the intercostal artery branching of the Adamkiewicz artery (ICA-AKA) and spinal cord ischemia (SCI) during thoracic endovascular aortic repair (TEVAR). Methods: Patients who underwent TEVAR from 2008 to 2022 were enrolled. Stent grafts covered the ICA-AKA in 108 patients (covered AKA group) and stent grafts didn't cover the ICA-AKA in 114 patients (uncovered AKA group). The characteristics of 58 patients from each group were matched based on propensity scores. Results: No significant differences in SCI rates were detected between the covered AKA (10%; 11/108) and uncovered AKA (3.5%; 4/114) groups (P = .061). Shaggy aorta (odds ratio [OR], 5.16; 95% confidence interval [CI], 1.74-15.3, P = .003), iliac artery access (OR, 6.81; 95% CI, 2.22-20.9, P = .001), and procedural time (OR, 1.01; 95% CI, 1.00-1.02, P = .003) were risk factors for SCI in the entire cohort. Although covering the ICA-AKA (OR, 2.60; 95% CI, 0.86-7.88, P = .058) was not a significant risk factor, shaggy aorta (OR, 8.15; 95% CI, 2.07-32.1, P = .003), iliac artery access (OR, 9.09; 95% CI, 2.22-37.2, P = .002), and procedural time (OR, 1.01; 95% CI, 1.01-1.02, P = .008) were risk factors for SCI in the covered AKA group. No significant risk factors were detected in the uncovered AKA group. Conclusions: Covering the ICA-AKA was not an independent risk for SCI in TEVAR. However, covering the ICA-AKA was indirectly associated with the risk of SCI in patients with shaggy aorta, iliac access, and procedural time.

A multicenter, single-arm, phase II clinical trial of adrenomedullin in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.

Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), the most common form of hereditary cerebral small vessel disease (SVD), currently lacks disease-modifying treatments. Adrenomedullin (AM), a vasoactive peptide with angiogenic, vasodilatory, anti-inflammatory, and anti-oxidative properties, shows potential effects on the neuro-glial-vascular unit. Objective: The AdrenoMedullin for CADASIL (AMCAD) study aims to assess the efficacy and safety of AM in patients with CADASIL. Sample size: Overall, 60 patients will be recruited. Methods: The AMCAD is a multicenter, investigator-initiated, single-arm phase II trial. Patients with a confirmed CADASIL diagnosis, based on NOTCH3 genetic testing, will receive an 8-h AM treatment (15 ng/kg/min) for 14 days following a baseline assessment (from day 1 to day 14). Follow-up evaluations will be performed on days 15, 28, 90, and 180. Study outcomes: The primary endpoint is the cerebral blood flow change rate in the frontal cortex, evaluated using arterial spin labeling magnetic resonance imaging, from baseline to day 28. Summary statistics, 95% confidence intervals, and a one-sample t-test will be used for analysis. Conclusion: The AMCAD study aims to represent the therapeutic potential of AM in patients with CADASIL, addressing an unmet medical need in this challenging condition. Clinical Trial Registration: jRCT 2,051,210,117 (https://jrct.niph.go.jp/en-latest-detail/jRCT2051210117).

Protein interaction networks characterizing the A549 cells Klotho transfected are associated with activated pro-apoptotic Bim and suppressed Wnt/ß-catenin signaling pathway.

Invasive assays and lung tumor-bearing mice models using a human lung adenocarcinoma cell line A549 cells transfected with the Klotho (KL) gene, A549/KL cells, have confirmed that KL suppresses invasive/metastatic potential. This study aimed to identify the co-expression protein networks and proteomic profiles associated with A549/KL cells to understand how Klotho protein expression affects molecular networks associated with lung carcinoma malignancy. A two-step application of a weighted network correlation analysis to the cells' quantitative proteome datasets of a total of 6,994 proteins, identified by mass spectrometry-based proteomic analysis with data-independent acquisition (DIA), identified one network module as most significantly associated with the A549/KL trait. Upstream analyses, confirmed by western blot, implicated the pro-apoptotic Bim (Bcl-2-like protein 11) as a master regulator of molecular networks affected by Klotho. GeneMANIA interaction networks and quantitative proteome data implicated that Klotho interacts with two signaling axes: negatively with the Wnt/ß-catenin axis, and positively by activating Bim. Our findings might contribute to the development of future therapeutic strategies.

[Fatal invasive pneumococcal disease developed 14 years after allogeneic hematopoietic stem cell transplantation in a patient with myelodysplastic syndrome].

Invasive pneumococcal diseases (IPDs) after allogeneic hematopoietic stem cell transplantation have high fatality rates and often develop late after transplantation. The patient was a 58-year-old female. Fourteen years ago, she underwent bone marrow transplantation from a HLA-DR 1-antigen mismatched unrelated donor for myelodysplastic syndrome. She developed pneumonia, chronic graft-versus-host disease, and hypogammaglobulinemia. She received 23-valent pneumococcal capsular polysaccharide vaccine 11 and 6 years earlier. She was presented to our emergency room with fever. Her blood culture was positive for pneumococcus, and she was diagnosed with an IPD. The patient received antibiotic treatment but died on the third day of hospitalization. Because of its seriousness, pneumococcal infection should receive attention even 10 or more years after transplantation. Preventive approaches such as vaccination and early intervention at the time of diagnosis are important.

Differential Reactivation of Cytomegalovirus and Epstein-Barr Virus in Patients with B Cell Lymphoma.

Although cytomegalovirus (CMV) and Epstein-Barr virus (EBV) are considered latent viruses, their reactivation occurs in immunosuppressed conditions. We previously reported that CMV and EBV are reactivated in patients receiving immunosuppressive therapy and/or chemotherapy. This retrospective, single-center study aimed to determine the frequency of viral reactivation and clinical characteristics of patients with B cell lymphoma (B-ML) receiving chemotherapy. Twenty-four patients (mean age 73 years, range 40-87 years; male-to-female ratio, 15:9) with diffuse large B cell lymphoma (n = 15), follicular lymphoma (n = 8), or mantle cell lymphoma (n = 1) were enrolled. Serum CMV and EBV DNA levels were analyzed using quantitative real-time polymerase chain reaction in patients with B-ML receiving chemotherapy. We determined the cumulative reactivation of each virus and analyzed the relationship between viral reactivation and clinical characteristics. Three patients experienced relapse or refractory (R/R) disease and the others had de novo lymphomas. The frequencies of CMV and EBV reactivations were 54.2% and 37.5%, respectively. CMV reactivation occurred significantly earlier during chemotherapy courses in R/R patients than in de novo patients (p = 0.0038), while EBV reactivation was frequently found before treatment. Baseline serum levels of soluble interleukin-2 receptor were higher (4318.0 vs. 981.1 U/mL, p = 0.010) and hemoglobin levels were lower (11.1 vs. 13.0 g/dL, p = 0.0038) in patients with EBV reactivation than in those without reactivation. These findings were not observed in patients with CMV reactivation. CMV reactivation was associated with iatrogenic immunosuppression, whereas EBV reactivation was related to immunosuppression by lymphoma, indicating that the mechanisms of these viral reactivations differed.

Construction of an Automatic Quantification Method for Bone Marrow Cellularity Using Image Analysis Software.

Although rapid, the evaluation of bone marrow (BM) cellularity is semi-quantitative and largely dependent upon visual estimates. We aimed to construct an automatic quantification method using image analysis software. We used hematoxylin and eosin (HE)-stained specimens of BM biopsies and clots from patients who underwent BM examination at Tottori University Hospital from 2020 to 2022. We compared image analysis (Methods A, B, and C) with visual estimates in pathology reports of 91 HE specimens in 54 cases (29 males, 25 females), including 38 biopsy and 53 clot specimens. Cellularity was visually scored as hypocellular (n = 17), normocellular (n = 44), or hypercellular (n = 30). Compared with the visual estimates, intraclass correlation coefficients for Methods A, B, and C were 0.80, 0.85, and 0.88, respectively. The most appropriate values were obtained with Method C which detected both non-fatty and cell nuclear areas.

Pulmonary artery blood flow dynamics in chronic thromboembolic pulmonary hypertension.

Chronic thromboembolic pulmonary hypertension is caused by incomplete resolution and organization of thrombi. Blood flow dynamics are involved in thrombus formation; however, only a few studies have reported on pulmonary artery blood flow dynamics in patients with chronic thromboembolic pulmonary hypertension. Furthermore, the effects of treatment interventions on pulmonary artery blood flow dynamics are not fully understood. The aim of the study was to evaluate pulmonary artery blood flow dynamics in patients with chronic thromboembolic pulmonary hypertension before and after pulmonary endarterectomy and balloon pulmonary angioplasty, using computational fluid dynamics. We analyzed patient-specific pulmonary artery models of 10 patients with chronic thromboembolic pulmonary hypertension and three controls using computational fluid dynamics. In patients with chronic thromboembolic pulmonary hypertension, flow velocity and wall shear stress in the pulmonary arteries were significantly decreased, and the oscillatory shear index and blood stagnation volume were significantly increased than in controls. Pulmonary endarterectomy induced redistribution of pulmonary blood flow and improved blood flow dynamics in the pulmonary artery. Balloon pulmonary angioplasty improved pulmonary blood flow disturbance, decreased blood flow stagnation, and increased wall shear stress, leading to vasodilatation of the distal portion of the pulmonary artery following balloon pulmonary angioplasty treatment.

Lower-profile stent graft reduces the risk of embolism during thoracic endovascular aortic repair in shaggy aorta.

OBJECTIVES: This study aimed to reveal the association between lower-profile stent graft (LPSG) and embolism during thoracic endovascular aortic repair for non-dissecting distal arch and descending thoracic aortic aneurysm. METHODS: This study reviewed data of 35 patients who underwent thoracic endovascular aortic repair with LPSG (27 males; age: 77 ± 9.2 years) and 312 who underwent thoracic endovascular aortic repair with conventional-sized stent graft (CSSG) (247 males; age: 77 ± 7.4 years) from 2009 to 2021. RESULTS: The rate of total embolic events was significantly lower in the LPSG group (0/35 [0%]) than the CSSG group (34/312 [11.2%]) (P = 0.035). Shaggy aorta (odds ratio: 5.220; P < 0.001) were identified as positive embolic event predictors. The rate of total embolic events in 68 patients with shaggy aorta (12 in LPSG/56 in CSSG) was significantly lower in the LPSG group (0/12 [0%]) than the CSSG group (19/56 [34%]) (P = 0.015). The rate of total embolic events in 279 patients with the non-shaggy aorta (23 in LPSG/256 in CSSG) reveals no difference between the 2 groups (0 [0%]/16 [6.3%]) (P = 0.377). CONCLUSIONS: LPSG usage could reduce embolism in thoracic endovascular aortic repair, and the difference was more pronounced in patients with the shaggy aorta. LPSG might be beneficial in preventing embolism in thoracic endovascular aortic repair for patients with a shaggy aorta.

Deep Learning-based Post Hoc CT Denoising for the Coronary Perivascular Fat Attenuation Index.

RATIONALE AND OBJECTIVES: Coronary inflammation related to high-risk hemorrhagic plaques can be captured by the perivascular fat attenuation index (FAI) using coronary computed tomography angiography (CCTA). Since the FAI is susceptible to image noise, we believe deep learning (DL)-based post hoc noise reduction can improve diagnostic capability. We aimed to assess the diagnostic performance of the FAI in DL-based denoised high-fidelity CCTA images compared with coronary plaque magnetic resonance imaging (MRI) delivered high-intensity hemorrhagic plaques (HIPs). MATERIALS AND METHODS: We retrospectively reviewed 43 patients who underwent CCTA and coronary plaque MRI. We generated high-fidelity CCTA images by denoising the standard CCTA images using a residual dense network that supervised the denoising task by averaging three cardiac phases with nonrigid registration. We measured the FAIs as the mean CT value of all voxels (range of -190 to -30 HU) located within a radial distance from the outer proximal right coronary artery wall. The diagnostic reference standard was defined as HIPs (high-risk hemorrhagic plaques) using MRI. The diagnostic performance of the FAI in the original and denoised images was assessed using receiver operating characteristic curves. RESULTS: Of 43 patients, 13 had HIPs. The denoised CCTA improved the area under the curve (0.89 [95% confidence interval (CI) 0.78-0.99]) of the FAI compared with that in the original image (0.77 [95% CI, 0.62-0.91], p = 0.008). The optimal cutoff value for predicting HIPs in denoised CCTA was -69 HU with 0.85 (11/13) sensitivity, 0.79 (25/30) specificity, and 0.80 (36/43) accuracy. CONCLUSION: DL-based denoised high-fidelity CCTA improved the AUC and specificity of the FAI for predicting HIPs.

Lung-to-heart ratio analysis using virtual planar images obtained from myocardial perfusion SPECT data: A phantom and clinical studies.

BACKGROUNDS: The lung-to-heart ratio (L/H ratio) in myocardial perfusion scintigraphy (MPS) is a useful marker that complements the sensitivity of ischemia detection. However, it requires planar imaging acquired following a separate protocol in addition to single-photon emission computed tomography (SPECT). We developed a novel method for constructing virtual planar image (VPI) from SPECT data. METHODS: Myocardial phantoms using Tl-201 were built with different amounts of radioactivity in the lungs. SPECT data and conventional planar images of these phantoms were collected with an Anger-type gamma camera. VPIs were constructed by adding all coronal images reconstructed from SPECT data. The clinical utility of VPIs obtained from 52 patients who underwent MPS with Tc-99m sestamibi was evaluated. RESULTS: The radioactivity linearity of VPIs was satisfactory, with a correlation coefficient of r ≥ .99 between the measured amounts of radioactivity and image counts. The L/H ratios obtained from VPI analysis were strongly correlated with those of conventional planar images with a correlation coefficient of r ≥ .99 in the phantom study and r = .929 in clinical application. CONCLUSION: The accuracy of VPI-based L/H ratio analysis was comparable to that of conventional planar image-based analysis. VPIs could be used as an alternative method of obtaining planar images in clinical settings.

Development of a Prognostic Scoring System using MYC Expression and Soluble Interleukin Receptor -2 level for Diffuse Large B-cell Lymphoma.

Background: Diffuse large B-cell lymphoma, not otherwise specified (DLBCL-NOS), is the most frequent type of lymphoid neoplasm. Methods: We investigated the relationships between clinical factors of DLBCL-NOS and MYC immunohistochemistry (IHC) staining. Results: A total of 110 patients diagnosed with DLBCL-NOS from 2012 to 2020 at Tottori University Hospital and treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) chemotherapy were included. IHC staining of MYC in formalin-fixed, paraffin-embedded tumor specimens was performed, and ROC-curve analysis revealed the cut-off value of the MYC positive rate as 55%. The 2-year overall survival (OS) rates of the MYC-negative and -positive groups were 84.7% vs 57.7% (P = 0.0091), and the progression-free survival rates were 77.8% vs 54.7% (P = 0.016), respectively. Multivariate analysis for OS showed prognostic significance of MYC positivity [hazards ratio (HR): 2.496; P = 0.032], and serum levels of soluble interleukin-2 receptor (sIL-2R) > 2000 U/mL (HR: 3.950; P = 0.0019), as well as age > 75 (HR: 2.356; P = 0.068). The original scoring system was developed based on these findings. By assigning one point to each item, age (> 75), MYC positivity, and sIL-2R level (> 2000), all patients were classified into three risk categories: group 1 (0 points), group 2 (1 point), and group 3 (2-3 points). The 2-year survival rates were 100%, 83.0%, and 47.1% for the groups 1, 2, and 3, respectively (P < 0.0001). Conclusion: We suggest that a prognostic scoring system using MYC expression and soluble interleukin receptor -2 level is useful for the prediction of prognosis, contributing to further stratification in DLBCL-NOS.

Fibrin monomer complex as a potential thrombosis marker related to venous thromboembolism risk in pregnant women.

BACKGROUND: Pregnancy is a risk factor for venous thromboembolism (VTE) due to increased coagulation factor activity and decreased protein S activity. However, thrombosis markers for predicting VTE in pregnancy remain controversial. This study aimed to investigate the relationship between VTE risk and thrombosis markers in pregnant women and to identify markers related to VTE risk. METHODS: Archived plasma samples from 107 pregnant women were used in this study, and the concentrations of D-dimer, fibrin monomer complex (FMC), plasmin-plasmin inhibitor complex, prothrombin time, activated partial thromboplastin time, and fibrinogen were measured. VTE risk was scored according to the Royal College of Obstetricians and Gynaecologists green-top guidelines and the patients were divided into low- or high-risk groups. RESULTS: The median (range) of risk score for deep vein thrombosis was 2 (0-8), and we defined the high-risk group included those with a score of ≧3. D-dimer and FMC concentrations were significantly higher in the high-risk group than in the low-risk group (D-dimer 4.5 vs 2.6 µg/mL, p = 0.008; FMC 14.6 vs 3.4 µg/mL, p < 0.001). Although D-dimer concentration significantly increased with gestational age (Spearman's correlation coefficient [rs] = 0.317, p < 0.001), FMC concentration did not (rs = -0.081, p = 0.409). The area under the receiver operating characteristic curve values of D-dimer, FMC, and both D-dimer and FMC for the high-risk group were 0.656, 0.713, and 0.738, respectively. CONCLUSIONS: FMC may be a thrombosis marker related to VTE risk in pregnancy and is potentially preferable over D-dimer concentrations.

Optimization of null point in Look-Locker images for myocardial late gadolinium enhancement imaging using deep learning and a smartphone.

OBJECTIVES: To determine the optimal inversion time (TI) from Look-Locker scout images using a convolutional neural network (CNN) and to investigate the feasibility of correcting TI using a smartphone. METHODS: In this retrospective study, TI-scout images were extracted using a Look-Locker approach from 1113 consecutive cardiac MR examinations performed between 2017 and 2020 with myocardial late gadolinium enhancement. Reference TI null points were independently determined visually by an experienced radiologist and an experienced cardiologist, and quantitatively measured. A CNN was developed to evaluate deviation of TI from the null point and then implemented in PC and smartphone applications. Images on 4 K or 3-megapixel monitors were captured by a smartphone, and CNN performance on each monitor was determined. Optimal, undercorrection, and overcorrection rates using deep learning on the PC and smartphone were calculated. For patient analysis, TI category differences in pre- and post-correction were evaluated using the TI null point used in late gadolinium enhancement imaging. RESULTS: For PC, 96.4% (772/749) of images were classified as optimal, with under- and overcorrection rates of 1.2% (9/749) and 2.4% (18/749), respectively. For 4 K images, 93.5% (700/749) of images were classified as optimal, with under- and overcorrection rates of 3.9% (29/749) and 2.7% (20/749), respectively. For 3-megapixel images, 89.6% (671/749) of images were classified as optimal, with under- and overcorrection rates of 3.3% (25/749) and 7.0% (53/749), respectively. On patient-based evaluations, subjects classified as within optimal range increased from 72.0% (77/107) to 91.6% (98/107) using the CNN. CONCLUSIONS: Optimizing TI on Look-Locker images was feasible using deep learning and a smartphone. KEY POINTS: • A deep learning model corrected TI-scout images to within optimal null point for LGE imaging. • By capturing the TI-scout image on the monitor with a smartphone, the deviation of the TI from the null point can be immediately determined. • Using this model, TI null points can be set to the same degree as that by an experienced radiological technologist.

A multicenter prospective randomized study comparing the incidence of periprocedural cerebral embolisms caused by catheter ablation of atrial fibrillation between cryoballoon and radiofrequency ablation (Embo-Abl study): Study design.

BACKGROUND: Although catheter ablation (CA) has become a standard therapeutic approach to atrial fibrillation (AF), it imposes a low but relevant risk of thromboembolic complications of around 0.5%-1%, including ischemic strokes, and has an additional risk of clinically silent cerebral embolisms (SCEs) of 10%-40%. Both cryoballoon (CB) and radiofrequency (RF) ablation are routinely used clinically worldwide, yet there are few prospective data comparing the incidence of cerebral embolism after CA of AF between CB and RF ablation. METHODS: The aim of the Embo-Abl study will be to compare the incidence of cerebral embolisms on 3 T diffusion-weighted image magnetic resonance imaging (MRI) after CA of AF between CB and RF ablation in patients with AF in a prospective, multicenter, open-label, controlled, randomized fashion. The primary endpoint of the Embo-Abl study will be the occurrence of MRI-detected SCE 1-3 days after CA. The patients will be registered and randomly assigned to either the CB or RF ablation group in a 1:1 ratio. The study cohort will include 230 patients with AF from a multicenter in Japan. RESULTS: The results of this study are currently under investigation. CONCLUSION: The Embo-Abl study will be the first to compare the incidence of periprocedural cerebral embolisms caused by CA of AF between CB and RF ablation in a prospective, multicenter, randomized, controlled fashion.

Deep learning-based noise reduction for coronary CT angiography: using four-dimensional noise-reduction images as the ground truth.

BACKGROUND: To assess low-contrast areas such as plaque and coronary artery stenosis, coronary computed tomography angiography (CCTA) needs to provide images with lower noise without increasing radiation doses. PURPOSE: To develop a deep learning-based noise-reduction method for CCTA using four-dimensional noise reduction (4DNR) as the ground truth for supervised learning. MATERIAL AND METHODS: \We retrospectively collected 100 retrospective ECG-gated CCTAs. We created 4DNR images using non-rigid registration and weighted averaging three timeline CCTA volumetric data with intervals of 50 ms in the mid-diastolic phase. Our method set the original reconstructed image as the input and the 4DNR as the target image and obtained the noise-reduced image via residual learning. We evaluated the objective image quality of the original and deep learning-based noise-reduction (DLNR) images based on the image noise of the aorta and the contrast-to-noise ratio (CNR) of the coronary arteries. Further, a board-certified radiologist evaluated the blurring of several heart structures using a 5-point Likert scale subjectively and assigned a coronary artery disease reporting and data system (CAD-RADS) category independently. RESULTS: DLNR CCTAs showed 64.5% lower image noise (P < 0.001) and achieved a 2.9 times higher CNR of coronary arteries than that in original images, without significant blurring in subjective comparison (P > 0.1). The intra-observer agreement of CAD-RADS in the DLNR image was excellent (0.87, 95% confidence interval = 0.77-0.99) with original CCTAs. CONCLUSION: Our DLNR method supervised by 4DNR significantly reduced the image noise of CCTAs without affecting the assessment of coronary stenosis.