Adult cardiomyocytes-derived EVs for the treatment of cardiac fibrosis.

Cardiac fibrosis is a common pathological feature of cardiovascular diseases that arises from the hyperactivation of fibroblasts and excessive extracellular matrix (ECM) deposition, leading to impaired cardiac function and potentially heart failure or arrhythmia. Extracellular vesicles (EVs) released by cardiomyocytes (CMs) regulate various physiological functions essential for myocardial homeostasis, which are disrupted in cardiac disease. Therefore, healthy CM-derived EVs represent a promising cell-free therapy for the treatment of cardiac fibrosis. To this end, we optimized the culture conditions of human adult CMs to obtain a large yield of EVs without compromising cellular integrity by using a defined combination of small molecules. EVs were isolated by ultracentrifugation, and their characteristics were analysed. Finally, their effect on fibrosis was tested. Treatment of TGFß-activated human cardiac fibroblasts with EVs derived from CMs using our culture system resulted in a decrease in fibroblast activation markers and ECM accumulation. The rescued phenotype was associated with specific EV cargo, including multiple myocyte-specific and antifibrotic microRNAs, although their effect individually was not as effective as the EV treatment. Notably, pathway analysis showed that EV treatment reverted the transcription of activated fibroblasts and decreased several signalling pathways, including MAPK, mTOR, JAK/STAT, TGFß, and PI3K/Akt, all of which are involved in fibrosis development. Intracardiac injection of CM-derived EVs in an animal model of cardiac fibrosis reduced fibrotic area and increased angiogenesis, which correlated with improved cardiac function. These findings suggest that EVs derived from human adult CMs may offer a targeted and effective treatment for cardiac fibrosis, owing to their antifibrotic properties and the specificity of cargo.

Super-Elderly Case of Acute Lower Limb Ischemia Treated with Indigo Aspiration System in Japan.

The Indigo Aspiration System (Penumbra Ltd., Alameda, CA, USA), a catheter-based device intended for the endovascular removal of clots from peripheral arteries and veins, was launched in Japan to treat acute limb ischemia after the cessation of urokinase sales. The initial application of this system in Japan was on a 96-year-old male patient. He was diagnosed with acute lower limb ischemia, which was caused by an embolism from a left common iliac artery aneurysm. The treatment significantly enhanced the perfusion to his left foot. This case report elaborates on the patient's treatment experience and discusses the indications for using the device.

The Impact of Chronic Limb-Threatening Ischemia on Cardiac Surgery.

Purpose: The effect of chronic limb threatening ischemia (CLTI) on advanced cardiac disease, which requires surgical treatment, has rarely been reported. The purpose of this study was to review the outcomes of cardiac surgery in patients with CLTI and determine the risk factors, with a particular focus on the severity of CLTI. Patients: The baseline characteristics and outcomes of 33 patients who were treated for CLTI and underwent cardiac surgery were retrospectively analyzed. The states of CLTI were evaluated based on the Wound, Ischemia, and foot Infection (WIfI) classification system, and 33 patients were divided into the low-WIfI group (stages 1-2, n = 13) and high-WIfI group (stages 3-4, n = 20). Results: The in-hospital mortality rate was 0% in low-WIfI group and 35% in high-WIfI group (p = 0.027). Postoperative complications, particularly severe infections, occurred more frequently among high-WIfI group than low-WIfI group (70.0% vs. 23.1%, p < 0.01). Multivariable analysis identified foot infection grade as a WIfI classification factor and lower albumin levels as factors significantly associated with postoperative complications. The 1-year and 2-year survival rates were 84.6% and 67.7% in low-WIfI group and 45% and 28.1% in high-WIfI group, respectively (p = 0.011). Conclusions: Cardiac surgery in patients with high WIfI stage was an extremely high-risk procedure. In such patients, lowering the WIfI stage by lower extremity revascularization and/or debridement of diseased parts prior to cardiac surgery can be considered.

Two High-Precision Proximity Capacitance CMOS Image Sensors with Large Format and High Resolution.

This paper presents newly developed two high-precision CMOS proximity capacitance image sensors: Chip A with 12 µm pitch pixels with a large detection area of 1.68 cm2; Chip B with 2.8 µm pitch 1.8 M pixels for a higher resolution. Both fabricated chips achieved a capacitance detection precision of less than 100 zF (10-19 F) at an input voltage of 20 V and less than 10 zF (10-20 F) at 300 V due to the noise cancelling technique. Furthermore, by using multiple input pulse amplitudes, a capacitance detection dynamic range of up to 123 dB was achieved. The spatial resolution improvement was confirmed by the experimentally obtained modulation transfer function for Chip B with various line and space pattens. The examples of capacitance imaging using the fabricated chips were also demonstrated.

Stent-Graft Removal and Extra-Anatomical Bypass for the Treatment of Stent-Graft Infection after Endovascular Aneurysm Repair.

Stent-graft infection is a rare but potentially life-threatening complication of endovascular aortic repair. There are currently no consensus guidelines for treating stent-graft infections, but surgical treatment is generally considered preferable due to the low overall survival rate of patients receiving conservative therapy; however, the revascularization method remains controversial. We report a case in which stent-graft infection after endovascular aneurysm repair was successfully treated by stent-graft removal and extra-anatomical bypass (EAB). EAB is an effective method of revascularization for stent-graft infection.

Challenges for the Development of Extracellular Vesicle-Based Nucleic Acid Medicines.

Nucleic acid drugs, such as siRNAs, antisense oligonucleotides, and miRNAs, exert their therapeutic effects by causing genetic changes in cells. However, there are various limitations in their delivery to target organs and cells, making their application to cancer treatment difficult. Extracellular vesicles (EVs) are lipid bilayer particles that are released from most cells, are stable in the blood, and have low immunogenicity. Methods using EVs to deliver nucleic acid drugs to target organs are rapidly being developed that take advantage of these properties. There are two main methods for loading nucleic acid drugs into EVs. One is to genetically engineer the parent cell and load the target gene into the EV, and the other is to isolate EVs and then load them with the nucleic acid drug. Target organ delivery methods include passive targeting using the enhanced permeation and retention effect of EVs and active targeting in which EVs are modified with antibodies, peptides, or aptamers to enhance their accumulation in tumors. In this review, we summarize the advantages of EVs as a drug delivery system for nucleic acid drugs, the methods of loading nucleic acid drugs into EVs, and the targeting of EVs to target organs.

Extracellular Vesicles Are Key Regulators of Tumor Neovasculature.

Tumor progression involves a series of biologically important steps in which the crosstalk between cancer cells and the surrounding environment is an important issue. Angiogenesis is a key tumorigenic phenomenon for cancer progression. Tumor-related extracellular vesicles (EVs) modulate the tumor microenvironment (TME) through cell-to-cell communication. Tumor cells in a hypoxic TME release more EVs than cells in a normoxic environment due to uncontrollable tumor proliferation. Tumor-derived EVs in the TME influence endothelial cells (ECs), which then play multiple roles, contributing to tumor angiogenesis, loss of the endothelial vascular barrier by binding to ECs, and subsequent endothelial-to-mesenchymal transition. In contrast, they also indirectly induce tumor angiogenesis through the phenotype switching of various cells into cancer-associated fibroblasts, the activation of tumor-associated ECs and platelets, and remodeling of the extracellular matrix. Here, we review current knowledge regarding the involvement of EVs in tumor vascular-related cancer progression.

Distal Bypass Grafting Using the Basilic-Cephalic Loop Vein for Chronic Limb-Threatening Ischemia under Peripheral Nerve Blockades in a Patient with Severely-Reduced Heart Function and End-Stage Renal Disease.

A 51-year-old man with severe comorbidities required redo revascularization due to left chronic limb-threatening ischemia caused by a previous vein graft occlusion. The saphenous veins were not available due to previous surgeries. Femoro-posterior tibial artery bypass surgery was successfully performed using the basilic-cephalic loop vein under peripheral nerve blockades. This anesthesia allowed a series of surgical revascularizations without general anesthesia, and the postoperative courses were uneventful. The patient survived for 4 years with ambulatory status. In conclusion, loop graft can be an alternative single vein material for distal bypass when no saphenous veins are available.

[Pericardial Hematoma Mimicking Pericardial Tumor;Report of a Case].

A case was diagnosed as pericardial tumor preoperatively, which was found to be pericardial hematoma and localized constrictive pericarditis intraoperatively. A pericardial hematoma resection and a pericardiectomy were performed.

[Trial of the Profit Optimization of the Department of Cardiac Surgery in the Local National University Hospital].

In recent years economic sense is required in hospital management, the national university hospital is also no exception. We performed duty improvement efforts as well as the current state analysis in the department of cardiac surgery for the purpose of revenue optimization in our hospital. At result, we succeeded in the improvement of the medical index as well as medical profit and found the key of solution to the serious problem that national university hospital has.