Extracellular Vesicles Derived from Type 2 Diabetic Mesenchymal Stem Cells Induce Endothelial Mesenchymal Transition under High Glucose Conditions Through the TGFß/Smad3 Signaling Pathway.

Type 2 diabetes mellitus (T2DM) is associated with endothelial dysfunction, which results in delayed wound healing. Mesenchymal stem cells (MSCs) play a vital role in supporting endothelial cells (ECs) and promoting wound healing by paracrine effects through their secretome-containing extracellular vesicles. We previously reported the impaired wound healing ability of adipose tissue-derived MSC from T2DM donors; however, whether extracellular vesicles isolated from T2DM adipose tissue-derived MSCs (dEVs) exhibit altered functions in comparison to those derived from healthy donors (nEVs) is still unclear. In this study, we found that nEVs induced EC survival and angiogenesis, whereas dEVs lost these abilities. In addition, under high glucose conditions, nEV protected ECs from endothelial-mesenchymal transition (EndMT), whereas dEV significantly induced EndMT by activating the transforming growth factor-ß/Smad3 signaling pathway, which impaired the tube formation and in vivo wound healing abilities of ECs. Interestingly, the treatment of dEV-internalized ECs with nEVs rescued the induced EndMT effects. Of note, the internalization of nEV into T2DM adipose tissue-derived MSC resulted in the production of an altered n-dEV, which inhibited EndMT and supported the survival of T2DM db/db mice from severe wounds. Taken together, our findings suggest the role of dEV in endothelial dysfunction and delayed wound healing in T2DM by the promotion of EndMT. Moreover, nEV treatment can be considered a promising candidate for cell-free therapy to protect ECs in T2DM.

Extracellular vesicles derived from SARS-CoV-2 M-protein-induced triple negative breast cancer cells promoted the ability of tissue stem cells supporting cancer progression.

Introduction: SARS-CoV-2 infection increases the risk of worse outcomes in cancer patients, including those with breast cancer. Our previous study reported that the SARS-CoV-2 membrane protein (M-protein) promotes the malignant transformation of triple-negative breast cancer cells (triple-negative BCC). Methods: In the present study, the effects of M-protein on the ability of extracellular vesicles (EV) derived from triple-negative BCC to regulate the functions of tissue stem cells facilitating the tumor microenvironment were examined. Results: Our results showed that EV derived from M-protein-induced triple-negative BCC (MpEV) significantly induced the paracrine effects of adipose tissue-derived mesenchymal stem cells (ATMSC) on non-aggressive BCC, promoting the migration, stemness phenotypes, and in vivo metastasis of BCC, which is related to PGE2/IL1 signaling pathways, in comparison to EV derived from normal triple-negative BCC (nEV). In addition to ATMSC, the effects of MpEV on endothelial progenitor cells (EPC), another type of tissue stem cells, were examined. Our data suggested that EPC uptaking MpEV acquired a tumor endothelial cell-like phenotype, with increasing angiogenesis and the ability to support the aggressiveness and metastasis of non-aggressive BCC. Discussion: Taken together, our findings suggest the role of SARS-CoV-2 M-protein in altering the cellular communication between cancer cells and other non-cancer cells inside the tumor microenvironment via EV. Specifically, M-proteins induced the ability of EV derived from triple-negative BCC to promote the functions of non-cancer cells, such as tissue stem cells, in tumorigenesis.

Twisting of HeartMate II outflow graft 2.5 years after implantation-HM2 is still ongoing.

A 47-year-old woman with dilated cardiomyopathy underwent HeartMate II (HM2) implantation as a bridge-to-transplantation. Her postoperative course was good. However, 2.5 years after surgery, the outflow graft was found to be twisted and the graft and pump was exchanged. While HeartMate 3(HM3) twisting of the outflow graft is well documented, such malfunctions in HM2 are almost unknown. Although HM2 has since been discontinued, there are a significant number of patients using HM2 who are awaiting heart transplants or destination therapy. We caution that, even with HM2, the possibility of late-phase twisting requires vigilance.

Large-view x-ray imaging for medical applications using the world's only vertically polarized synchrotron radiation beam and a single asymmetric Si crystal.

Objective.X-ray microangiography provides detailed information on the internal structure and function of a biological subject. Its ability to evaluate the microvasculature of small animals is useful for acquiring basic and clinical medical knowledge. The following three conditions are necessary to attain detailed knowledge of biological functions: (1) high temporal resolution with sufficient x-ray intensity, (2) high spatial resolution, and (3) a wide field of view. Because synchrotron radiation microangiography systems provide high sapatial resolution and high temporal resolution as a result of their high x-ray intensity, such systems have been developed at various synchrotron radiation facilities, starting with the photon factory, leading to numerous medical discoveries. However, the three aforementioned functions are incompatible with the use of synchrotron radiation because the x-ray intensity decreases when a wide field of view is obtained. To overcome these problems, we developed a new x-ray optical system for microangiography in rats using synchrotron radiation x-rays.Approach.Instead of using monochromatic synchrotron radiation x-rays with a conventional double-crystal monochromator, we used white synchrotron radiation x-rays and an asymmetric Si crystal to simultaneously monochromatize the beam and widen the field of view.Main results.The intensity profile and spatial resolution of the x-ray images were then evaluated. The proposed x-ray optics increased the x-ray intensity and beam width by factors of 1.3 and 2.7, respectively, compared with those of conventional monochromatic x-rays. In addition,in vivostudies on microangiography in rats were performed to confirm that the images had sufficient intensity, spatial resolution, and field of view. One of a series of images taken at 50 ms frame-1was shown as an example.Significance.This x-ray optics provides sufficient x-ray intensity, high spatial resolution, and a wide field of view. This technique is expected providing new insights into the evaluation of the vascular system.

Total arch replacement with both frozen elephant trunk and transthoracic aorto-axillary extra-anatomical bypass through partial sternotomy for acute aortic dissection in a tracheostomy patient.

Median sternotomy near an existing tracheostoma risks deep sternal wound infection after cardiac surgery. We present herein a case of acute type A aortic dissection in a patient with a permanent tracheostoma after laryngectomy. Total arch replacement with both frozen elephant trunk and extra-anatomical bypass for supra-aortic trunks was performed through T-shaped partial sternotomy, resulting in recovery without deep sternal wound infection.

Two cases of catastrophic deterioration and multiple leaflet detachment in Trifecta valves.

Reports of early and catastrophic acute structural valve deterioration (SVD) in Trifecta valve (Abbott, St Paul, MN, USA) with multiple leaflet detachment are rare. We encountered two cases of early SVD in Trifecta valve with tears on two leaflets. Both cases presented with acute heart failure because of aortic insufficiency, and underwent redo aortic valve replacement; one patient died due to multiple organ failure caused by cardiogenic shock. Durability issues with the Trifecta valves; thus, necessitates long-term vigilance in aortic replacement patients.

The effect of roller head pump on platelet deterioration during the simulated extracorporeal circulation.

Roller pumping results in hemolysis and adverse effects on coagulation, but there are few reports on the influence of roller heads on platelets. Here, we evaluate the interaction between roller pumping and platelet function using a simulated extracorporeal circuit incorporating a vinyl chloride tube and roller head pump with 30 min recirculation. Platelet aggregation, platelet count, microparticle, P-selectin, Phosphatidylserine (PS) exposure and Ricinus Communis Agglutinin 1 (RCA-1) were measured before, 5, 10, 20, and 30 min after the recirculation using 100 ml of fresh human blood that had obtained from healthy volunteers (n = 9). Platelet aggregation and platelet count gradually decreased but microparticles significantly increased after the recirculation (P < 0.05). P-selectin, PS exposure and RCA-1 were measured using flow cytometry. There were no significant differences in the P-selectin and PS exposure expression during recirculation. RCA-1, a platelet apoptosis markers, significantly increased 30 min after recirculation (P < 0.05). We thus conclude that roller pumping induced platelet apoptosis and caused decreases in platelet count and aggregation after the recirculation.

Aortic annular enlargement techniques using an original patch for prosthetic valve endocarditis.

BACKGROUND: Prosthetic valve endocarditis (PVE) is a serious complication, and it is difficult to treat marked adhesion and infectious tissue. CASE PRESENTATION: There were four patients with aortic PVE, whose ages ranged from 59 to 80 years. In all patients, transoesophageal echocardiography revealed periannular abscess formation. We applied aortic annular enlargement techniques using a composite three-layer patch to repair the defects after radical debridement of the abscesses, and then replaced the prosthetic valves on the reconstructed annuli. All patients received antibiotics after surgery and recovered well without recurrence. CONCLUSIONS: The aortic annular enlargement techniques provided a good field of vision at the complicated annulus, and our original patch was useful for repairing the aortic annulus and its surrounding apparatus.

Slit Orifice Aortic Cusp Extension Technique for Small Bicuspid Valves.

We describe a modification to the aortic cusp extension technique that eliminates aortic regurgitation in pediatric small bicuspid valves. This simple and reproducible cusp extension technique secures coaptation and commissure suspension of the reconstructed aortic valve and may act as a bridge option for forthcoming reoperations.

Surgical Resection of an Adventitial Cyst of the Right Brachiocephalic Vein.

Adventitial cystic disease is an uncommon vascular anomaly known to occur in peripheral vessels but mediastinal appearances are extremely rare. Herein, we report the case of an adventitial cyst occurring in the right brachiocephalic vein which might have been associated with ovarian hyperstimulation syndrome.

Pulmonary Embolism Caused by Intravenous Leiomyosarcoma of the Lower Limb.

Pulmonary embolism (PE) is usually caused by thrombosis or tumor. We report the long-term survival of a patient with PE due to a leiomyosarcoma in the deep vein. A 71-year-old woman complained of dyspnea and swelling of the left lower limb. Computed tomography revealed filling defects in the pulmonary arteries and deep vein. She was diagnosed with PE caused by venous thrombosis and treated with anticoagulant therapy. Her symptoms were prolonged, and D-dimer tests remained negative. Biopsy of the substance in the deep vein revealed leiomyosarcoma. The possibility of PE caused by extravascular or intravascular tumors should be considered when a patient is negative for D-dimer.

Transaortic septal myectomy using direct septal echography.

We applied direct septal echography in transaortic septal myectomy for left ventricular outflow tract obstruction due to hypertrophic obstructive cardiomyopathy and asymmetric septal hypertrophy. A small L-shaped probe was inserted into the right ventricle through a 2-cm incision on the right ventricular outflow tract. The probe was placed directly on the interventricular septum to visualize its actual thickness. It was also helpful to push and expose the septum into a direct field of vision through the aortic annulus. This type of direct septal echography can be useful for the successful performance of transaortic septal myectomy.

Mediastinal Abscess Caused by an Expanded Polytetrafluoroethylene Membrane.

A 76-year-old man who had undergone tricuspid annuloplasty 13 years earlier was admitted to our hospital because of a high fever. Although he was treated with antibiotics for pneumonia, a mild fever persisted. Computed tomography and gallium scintigraphy revealed a mediastinal abscess with an expanded polytetrafluoroethylene (ePTFE) membrane. There were no positive cultures or sternal changes indicating poststernotomy mediastinitis. The membrane was removed by a left parasternal approach without resternotomy, and its total removal was essential for the patient's recovery. This is the first reported case of sterile mediastinal abscess caused by an ePTFE membrane after a cardiac operation.

[Aortic Valve Replacement Concomitant with Right and Left Ventricular Outflow Tract Repair Eight Years after Arterial Switch Operation for Double Outlet Right Ventricle;Report of a Case].

We report a case of successful aortic valve replacement and relief of right and left ventricular outflow tract obstruction 8 years after an arterial switch operation for double outlet right ventricle. Since the surgical access to the ascending aorta was limited because of the anatomical feature and the adhesion after the arterial switch operation, arterial infusion site for cardiopulmonary bypass was secured at the right common carotid artery ahead of the sternal re-entry. After cardiopulmonary bypass was established, the right pulmonary artery was divided and then dissection of the ascending aorta was completed to secure the space for aortic valve replacement. A discrete membrane of the left ventricular outflow and muscle bands of the right ventricular outflow were completely resected. The right pulmonary artery was reconstructed by interpose of a prosthetic graft. Our experience would provide a technical option how to handle complex late complications after the arterial switch operation.

Intractable Electrical Storm After Coronary Artery Bypass Grafting Originating in Abnormal Purkinje Fibers.

Electrical storm is a rare but critical complication following revascularization in patients with ischemic heart disease. We report the case of a 67-year-old man who developed drug refractory intractable electrical storm after emergent coronary artery bypass grafting for ischemic cardiomyopathy. The electrical storm was successfully eliminated by percutaneous endocardial radiofrequency catheter ablation targeting the abnormal Purkinje-related triggering ventricular premature contractions in a low-voltage zone.

Open surgical repair for a ruptured abdominal aortic aneurysm with a horseshoe kidney.

Horseshoe kidney is a congenital anomaly characterized by medial fusion of the bilateral kidneys. Treatment for an abdominal aortic aneurysm (AAA) with a horseshoe kidney is a technical challenge because of the complex anatomy. We report a successful open surgical repair for a ruptured AAA with a horseshoe kidney. An aortic grafting was performed with division of the renal isthmus through a transperitoneal approach. In the case of a ruptured AAA, quick open surgery is the most reliable treatment. If a horseshoe kidney coexists, transperitoneal approach with division of the renal isthmus provides good surgical field for an aortic grafting.

Left Ventricular Perforation during Catheter Ablation in a Patient with Idiopathic Thrombocytopenic Purpura.

Preoperative gamma-globulin therapy was recently performed to prevent bleeding complications in a patient with concomitant idiopathic thrombocytopenic purpura undergoing cardiac surgery. Here we report the case of a 75-year-old male patient with idiopathic thrombocytopenic purpura, chronic aortic dissection, and funnel chest in whom a left ventricular perforation sustained during catheter ablation was repaired during emergent surgery. Despite preoperative gamma-globulin therapy not being performed, bleeding complications were prevented because platelets were preserved by avoidance of cardiopulmonary bypass use. Although the funnel chest made it difficult to secure the operative field, the deep pericardial sutures were effective in repairing the perforation without cardiopulmonary bypass.

Right atrial myxoma with a large tumor embolus in the left pulmonary artery.

Cardiac myxoma, the most common primary cardiac tumor, usually develops in the left atrium. Right atrial myxomas are rare, especially those accompanied by pulmonary tumor embolism. We describe a case of a right atrial myxoma with a large tumor embolus in the left pulmonary artery. A 74-year-old man was referred to our hospital for the treatment of a right atrial tumor. Upon echocardiography, the right atrial tumor was revealed to have a mobile and tail-like surface projection. In addition, computed tomography showed that an embolus was wedged into the left pulmonary artery. We performed an emergency surgery to remove both the right atrial tumor and the pulmonary embolus. Histopathological examination revealed them both to be myxoma. Right atrial myxoma with a large pulmonary tumor embolus is a serious condition and emergency surgery to remove both cardiac tumors and pulmonary emboli should be performed to avoid the risk of sudden death.

Nontraditional placement of an implantable cardioverter-defibrillator in a heterotaxy patient after the completion of total cavopulmonary connection.

A 15-year-old boy with heterotaxy syndrome developed a prolonged QT interval and intractable torsade de pointes after the administration of sodium channel blockers for atrial tachyarrhythmia. Although this situation called for the placement of an implantable cardioverter-defibrillator, a conventional transvenous approach was not available since the patient had previously undergone a nonfenestrated extracardiac total cavopulmonary connection. We were urged to carry out the surgical placement of an epicardial lead for an implantable cardioverter-defibrillator using a single coil transvenous shock lead through re-do midline sternotomy. Here we describe the details of this nontraditional surgical procedure for the placement of a lead for an implantable cardioverter-defibrillator in a case without venous access into the heart.