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.

Effect of direct oral anticoagulant therapy on pulmonary artery clot dissolution in intermediate high-risk pulmonary thromboembolism.

BACKGROUND: Direct oral anticoagulants are the established drugs for treating pulmonary thromboembolism. The advantage of direct oral anticoagulants over conventional therapy for clot lysis and right ventricular unloading in the acute phase remains unclear. This study aimed to evaluate the effect of acute treatment with direct oral anticoagulants on clot dissolution and right ventricular unloading in intermediate high-risk pulmonary thromboembolism. METHODS: Thirty patients with intermediate high-risk pulmonary thromboembolism admitted between November 2012 and December 2018 were included; 21 and 9 were treated with direct oral anticoagulants and conventional therapy, respectively. We compared the efficacy of clot dissolution and right ventricular unloading for intermediate high-risk pulmonary thromboembolism between direct oral anticoagulant and conventional therapy in the acute phase. Efficacy was assessed by computed tomography obstruction index, right/left ventricular ratio, and brain natriuretic peptide levels between baseline and at discharge. RESULTS: Computed tomography obstruction index, right ventricular/left ventricular ratio, and brain natriuretic peptide levels were significantly lower at discharge than at admission in both groups. The rate of improvement in computed tomography obstruction index was significantly higher in the direct oral anticoagulant therapy group than in the conventional therapy group (64 ± 15% vs. 47 ± 16%; p = 0.01). There were no significant differences in the rate of improvement in right ventricular/ left ventricular ratio and brain natriuretic peptide levels between the two groups. CONCLUSIONS: Compared with conventional therapy, direct oral anticoagulants significantly reduced pulmonary artery clot burden conventional therapy in the acute treatment of intermediate high-risk pulmonary thromboembolism.

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.

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.

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.

Two Cases of Children With Black Hairy Tongue and Tooth Discoloration Caused by Antibacterial Agents.

Black hairy tongue (BHT) is a lesion in which the filiform papillae of the tongue are significantly extended by hyperkeratosis, thereby giving the tongue a hairy appearance. Here, we report two rare cases of children with BHT and tooth discoloration caused by antimicrobial agents. Case 1: A four-year-old female patient received intravenous linezolid after spinal surgery, and BHT developed on day eight of treatment. Subsequently, the patient developed teeth discoloration. Linezolid was continually administered for 50 days, and BHT and teeth discoloration improved 10 days after the end of linezolid treatment. Case 2: A two-year-old male patient with a brain abscess received intravenous meropenem and vancomycin. On the fourth day of treatment, BHT developed, and teeth discoloration was subsequently observed. Antibiotic therapy was continued for 82 days, and BHT and tooth discoloration improved 20 days after the treatment was discontinued.

Balloon pulmonary angioplasty for chronic thromboembolic pulmonary disease without pulmonary hypertension.

Balloon pulmonary angioplasty (BPA) is beneficial for patients with chronic thromboembolic pulmonary disease (CTEPD) with pulmonary hypertension (PH). However, the clinical benefit of BPA for the patients with CTEPD without PH remains unknown. In this study, we aimed to evaluate the efficacy, safety, and long-term outcomes of BPA in patients with CTEPD without PH. We retrospectively analyzed the data from 84 CTEPD patients with mean pulmonary artery pressure (mPAP) < 25 mmHg and 39 CTEPD patients with mPAP ≤ 20 mmHg (without PH). Among the 39 patients with CTEPD without PH, 14 underwent BPA (BPA-treated group), and the remaining 25 received no treatment (untreated group). In the patients with CTEPD without PH, BPA led to improvements in symptoms, pulmonary vascular resistance (3.6 ± 1.6 to 2.6 ± 1.1 Wood units, p < 0.001), peak oxygen consumption (16.1 ± 4.0 to 18.8 ± 4.3 mL/kg/min, p = 0.033), minute ventilation versus carbon dioxide production slope (41.4 ± 12.2 to 35.1 ± 6.7, p = 0.026), and mPAP/cardiac output slope (7.0 ± 2.6 to 4.4 ± 2.0 mmHg/L/min, p = 0.004) and facilitated the discontinuation of home oxygenation therapy, with no serious complications. Kaplan-Meier analysis showed no significant difference in all-cause mortality between the untreated and BPA-treated groups. BPA may be a safe treatment option for the patients with CTEPD without PH that can alleviate symptoms, improve exercise capacity, and facilitate weaning from home oxygen therapy. Further prospective randomized trials are needed to confirm these findings.

Laterality of CT-measured hepatic extracellular volume fraction in patients with chronic thromboembolic pulmonary hypertension.

PURPOSE: This study examines the hepatic extracellular volume fraction (ECV) disparity between the left and right lobes (ECV_left and ECV_right) in patients with chronic thromboembolic pulmonary hypertension (CTEPH), its association with right heart catheterization (RHC) metrics, and with intolerance to increased pulmonary hypertension (PH)-targeted medication dosages. METHODS: We retrospectively analyzed 72 CTEPH-diagnosed patients who underwent equilibrium-phase abdominal dual-energy CT (DECT) and RHC. Hepatic ECVs, derived from DECT's iodine maps using circular regions of interest in the liver and aorta, were correlated with RHC parameters via Spearman's rank correlation and lobe differences through the Wilcoxon signed-rank test. Logistic regression assessed cases with ECV_left exceeding ECV_right by > 0.05, while receiver operating characteristic curve analysis gauged ECVs' predictive power for medication intolerance. RESULTS: Of the 72 patients (57 females; median age 69), ECV_total (0.24, IQR 0.20-0.27) moderately correlated with RHC parameters (rs = 0.28, -0.24, 0.3 for mean pulmonary arterial pressure, cardiac index [CI], and pulmonary vascular resistance index, respectively). ECV_left significantly surpassed ECV_right (0.25 vs. 0.22, p < 0.001), with a greater ECV_left by > 0.05 indicating notably lower CI (p < 0.001). In 27 patients on PH medication, ECV_left effectively predicted medication intolerance (AUC = 0.84). CONCLUSION: In CTEPH patients, hepatic ECV correlated with RHC metrics, where elevated left lobe ECV suggested reduced CI and potential medication intolerance.

Feasibility of revascularization after gelatin sponge embolization for hemoptysis during balloon pulmonary angioplasty.

BACKGROUND: Vessel injury is a common complication during balloon pulmonary angioplasty (BPA). For persistent hemoptysis, gelatin sponge embolization (GSE) is considered, but its impact on subsequent perfusion in embolized vessels remains unknown. This study explores the feasibility of revascularization in vessels post-GSE. METHODS: We included 64 vessels from 50 patients with chronic thromboembolic pulmonary hypertension who experienced hemoptysis during BPA in 2012-2023. Twenty-four vessels were treated conservatively (conservative group), while 40 were treated with GSE for persistent hemoptysis or desaturation despite conservative treatment (GSE group). We assessed hemoptysis-related parameters, perfusion of injured vessels pre- and post-treatment, and hemodynamic parameters through multiple BPA sessions. RESULTS: Hemoptysis resolved immediately after the procedure in 67% of patients, including 70% of those in the GSE group, and all cases resolved by the next day. Of 37 embolized vessels, 41% showed spontaneous perfusion improvement in subsequent sessions. BPA was reperformed in 22 embolized vessels, with 86% showing further improvement, resulting in 70% of all embolized vessels finally showing improvement in perfusion. In both groups, clinical and hemodynamic parameters significantly improved after BPA. CONCLUSIONS: Perfusion of embolized vessels improved after GSE, suggesting that GSE is safe for the treatment of severe persistent hemoptysis after conservative treatment.

Comparative analysis of peri-nidal cerebral blood flow and metabolism using a novel quantitative 15O-PET method in patients with arteriovenous malformations.

To effectively treat cerebral arteriovenous malformations (AVMs), peri-nidal flow regulation and metabolic status must be understood. In this study, we used 15O-oxygen positron emission tomography (PET) post-processing analysis to investigate vascular radioactivity in the nidal region of AVMs. Single-dynamic PET imaging was performed on seven unruptured AVM patients during the sequential inhalation of 15O2 and C15O2. A previously validated dual-tracer basis function method (DBFM) was employed to calculate parametric images. The results of our study were as follows. First, in remote and contralateral AVM regions, DBFM and a previous approach of dual-tracer autoradiography (DARG) showed strong positive correlations in cerebral blood flow (CBF), cerebral oxygen metabolism rate (CMRO2), and oxygen extraction fraction. Second, peri-nidal CBF and CMRO2 correlation was lower, and overestimation occurred with DARG compared to with DBFM. Third, on comparing DBFM to quantitative 123I-iodoamphetamine single-photon emission computed tomography (SPECT), CBF correlated significantly. In contrast, the correlation between DARG and quantitative 123I-iodoamphetamine-SPECT was weaker in the peri-nidal regions. Fourth, analysis of tissue time-activity curves demonstrated good reproducibility using the novel formulation in the control, peri-nidus, and core nidal regions, indicating the adequacy of this approach. Overall, the DBFM approach holds promise for assessing haemodynamic alterations in patients with AVMs.

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.

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).