Quality of epicardial adipose tissue predicts major adverse cerebral and cardiovascular events following transcatheter aortic valve implantation.

Epicardial adipose tissue (EAT) have been shown to be associated with several heart disease, including coronary artery disease (CAD), atrial fibrillation (AF), and heart failure (HF). It is reported that the quality of EAT, represented by fat attenuation determined using computed tomography (CT) imaging, can detect the histologically-assessed remodeled EAT. We tested the hypothesis that quality of EAT would predict major adverse cerebral and cardiovascular events (MACCE) following transcatheter aortic valve implantation (TAVI) in patients with aortic stenosis (AS). A total of 125 consecutive severe AS patients who underwent TAVI were enrolled (39 male, mean 85.4 ± 4.0 years). Using CT imaging before TAVI, we measured the average CT fat attenuation of EAT (EAT attenuation) and investigated the association with MACCE. During the mean follow up period of 567 ± 371 days, 21 cases of MACCE were observed. Patients with MACCE had greater levels of EAT attenuation compared to those without (- 74 ± 3.7 Hounsfield Units (HU) vs - 77 ± 5.5 HU, p = 0.010). Based on the ROC curves, the high EAT attenuation was defined as > - 74.3 HU. According to this cut-off index, 44 patients were classified into the high EAT attenuation group (28 female, mean age 87 ± 3.6 years), whereas 81 patients were classified into the low EAT attenuation group (13 female, 85 ± 4.1 years). Kaplan-Meier survival curve demonstrated that the patients in the high EAT attenuation group showed greater prevalence of MACCE (log-rank 6.64, p = 0.010). Cox proportional hazards regression analysis revealed that EAT attenuation and Logistic EuroSCORE were independently associated with the incidence of MACCE. Our results suggest that quality of EAT, assessed by EAT attenuation detected by CT imaging, can predict the cerebral and cardiovascular events after TAVI in patients with AS.

A Molecule Having 13 Unpaired Electrons: Magnetic Property of a Gadolinium(III) Complex Coordinated with Six Nitronyl Nitroxide Radicals.

A gadolinium(III) complex coordinated with six nitronyl nitroxide radicals showed intriguing temperature-dependent changes in magnetic susceptibilities. The gadolinium(III) ion in the complex is pseudo-eight-coordinated by three singlet-ground-state diradical anion species based on nitronyl nitroxide radicals. The magnetic susceptibility (χpT) of the gadolinium(III) complex at 298 K, whose value corresponded to that of a system with 13 unpaired electrons (seven-spin system), decreased upon a lowering of the temperature to 11 K but increased upon a further lowering of the temperature. Finally, the χpT value at 2 K was found to be higher than that at room temperature. The temperature-dependent magnetic behavior could be explained by a structural change in the diradical anion ligand due to its flexibility.

Proposal criteria of paradoxical low-flow low-gradient aortic stenosis for predicting prognosis in patients undergoing transcatheter aortic valve implantation.

BACKGROUND: Paradoxical low-flow, low-gradient (PLF-LG) aortic stenosis (AS) is associated with poor prognosis in patients undergoing transcatheter aortic valve implantation (TAVI). This study aimed to verify the conventional criteria of PLF-LG AS (left ventricular ejection fraction [LVEF] > 50%, mean aortic valve pressure gradient [AVPG] < 40 mm Hg and stroke volume index [SVI] < 35 ml/m2 by measuring Doppler method) compatible for predicting prognosis in patients undergoing TAVI. MATERIALS AND METHODS: A total of 128 consecutive patients who underwent TAVI for AS with LVEF > 50% were enrolled. The primary endpoint was the hospital readmission due to heart failure (HRHF) and the secondary endpoint was all-cause mortality after hospital discharge. The patients were classified by both the conventional criteria of PLF-LG AS and the proposal criteria of PLF-LG AS if mean aortic valve pressure gradient (AVPG) < 40 mmHg and SVI by measuring Simpson's method < cut off value based on the ROC curve for predicting HRHF. RESULTS: According to the conventional criteria, only 6 patients were diagnosed with PLF-LG AS. However, according to the proposal criteria, 16 patients were diagnosed with PLF-LG AS. Fourteen patients developed HRHF during the follow-up period after TAVI. Based on the ROC curves, SVI by measuring Simpson's method (cut off value = 25 ml/m2) had higher sensitivity and specificity for predicting HRHF (AUC = 0.74, p = 0.0013) than SVI by measuring Doppler method (AUC = 0.63, p = 0.045). The multivariate analysis revealed that PLF-LG AS defined by the proposal criteria (HR: 5.25; 95% CI: 1.60-17.16; p = 0.0073) but not by the conventional criteria was independently associated with HRHF. PLF-LG AS defined by the conventional criteria and the proposal criteria were not associated with all-cause mortality in the univariate analysis. CONCLUSIONS: Our results demonstrated that new criteria of PLF-LG AS defined as SVI < 25 ml/m2 measured by Simpson's method could predict HRHF in patients with severe AS who underwent TAVI.

Extensive Aortic Stent Graft Coverage for Thoracoabdominal Aortic Aneurysm is Associated With Hemorrhagic Complications Induced by Disseminated Intravascular Coagulation.

BACKGROUND: Hybrid endovascular repair for thoracoabdominal aortic aneurysm (TAAA) is a less invasive alternative treatment than conventional open repair. However, disseminated intravascular coagulation (DIC) and hemorrhagic complications can occur postoperatively. We investigated risk factors for hemorrhagic complications after hybrid endovascular TAAA repair. METHODS: Sixty-one patients who underwent elective hybrid endovascular TAAA repair between 2007 and 2020 were included. Laboratory data before and after placing stent graft were collected, and DIC was diagnosed using a scoring system established by the Japanese Association for Acute Medicine. The length of the stent graft used to cover the aorta was defined as the aortic coverage length, which was measured using the first postoperative computed tomography image. Predictors of unexpected hemorrhagic complications were evaluated. RESULTS: Postoperative thrombocytopenia was observed in 57 (93%) patients, and their platelet count decreased significantly after stent graft placement (14.3 [9.5-18.0] vs. 8.2 [5.4-10.9] × 104/µL, P < 0.001). Fifteen (25%) and 45 patients (74%) were diagnosed with DIC before and after stent graft placement, respectively. Hemorrhagic complications were observed in 21 patients (34%). Multivariate logistic regression analysis revealed that aortic coverage length was an independent risk factor for hemorrhagic complications (odds ratio 1.441/50 mm increase; 95% confidence interval, 1.041-1.994, P = 0.027). The cutoff value for aortic coverage length obtained from the receiver operating characteristic curve (area under the curve = 0.72) was 304.4 mm (sensitivity 0.76, specificity 0.70). CONCLUSION: Aortic coverage length is a risk factor for hemorrhagic complications. Patients undergoing extensive aortic coverage greater than 304 mm should be closely monitored.

Three-month outcomes of aortic valve reconstruction using collagenous membranes (biosheets) produced by in-body tissue architecture in a goat model: a preliminary study.

BACKGROUND: Autologous pericardium is widely used as a plastic material in intracardiac structures, in the pulmonary artery, and in aortic valve leaflets. For aortic valve reconstruction (AVRec) using the Ozaki procedure, it has produced excellent clinical results over a 10-year period. In-body tissue architecture (iBTA), which is based on the phenomenon of tissue encapsulation of foreign materials, can be used to prepare autologous prosthetic tissues. In this preliminary study, we examined whether biosheets can be used as valve leaflet material for glutaraldehyde-free AVRec by subchronic implantation experiments in goats and evaluated its performance compared with glutaraldehyde-treated autologous pericardium for AVRec. METHODS: Biosheets were prepared by embedding molds for two months into the dorsal subcutaneous spaces of goats. Autogenic biosheets (n = 4) cut into the shape of the valve were then implanted to the aortic valve annulus of four goats for three months without glutaraldehyde treatment. Autologous pericardium (n = 4) was used in four goats as a control. Valve function was observed using echocardiography. RESULTS: All goats survived the three-month study period. With biosheets, the leaflet surfaces were very smooth and, on histology, partially covered with a thin neointima (including endothelial cells). Biosheets were more thoroughly assimilated into the aortic root compared with autologous pericardium. CONCLUSIONS: For the first time, biosheets were used for large animal AVRec. Biosheets could function as leaflets in the aortic position and may have the ability to assimilate into native valves.

Gorget-like Cuddling Suture: An Anastomosis Reinforcement Technique to Reduce Suture Bleeding for Aortic Surgery.

We developed a new reinforcement technique, the Gorget-like Cuddling (GOCU) suture, to prevent suture line bleeding during aortic surgery. After continuous aortic anastomosis with thick outer felt, an additional 2-0 Ticron (Medtronic, Minneapolis, MN) suture is placed distal from the first suture line. This GOCU suture directly holds the needle holes. Wall tension on the anastomosis can also be reduced to prevent longitudinal dilatation of the aorta. This technique can contribute to hemostasis for a fragile aortic wall in cases like acute aortic dissection.

Contribution of anti-inflammatory and anti-virulence effects of azithromycin in the treatment of experimental Staphylococcus aureus keratitis.

BACKGROUND: We aimed to demonstrate the contribution of anti-inflammatory and anti-virulence effects of azithromycin (AZM) in ocular surface infection treatment. METHODS: Staphylococcus aureus was injected into the corneal stroma of rabbits to induce keratitis. AZM at concentrations of 0.01, 0.1, and 1% was instilled into the eye twice daily. The eyes were examined using a slit lamp and scored. The viable bacteria in the cornea were counted at 48 h post infection. To evaluate the anti-inflammatory efficacy of AZM, S. aureus culture supernatant-induced anterior ocular inflammation in rabbit was examined using a slit lamp and scored. To evaluate the inhibitory effect of AZM on bacterial toxin production, S. aureus was cultured with AZM and hemolytic reaction in the culture supernatant was determined. RESULTS: In the bacterial keratitis model, AZM dose-dependently inhibited the increase in the clinical score. The viable bacterial count in the cornea treated with 1% AZM significantly decreased compared with that of the vehicle, whereas bacterial count in 0.01 and 0.1% AZM-treated corneas was similar to that of the vehicle. In the anterior ocular inflammation model, 0.1 and 1% AZM inhibited the increase in the clinical score. AZM inhibited hemolytic reaction at concentrations that did not inhibit bacterial growth. CONCLUSIONS: The results demonstrated that AZM has not only anti-bacterial, but also anti-inflammatory effects, and inhibits bacterial toxin production leading to ocular surface damage in bacterial infection. Thus, the therapeutic effect of AZM against ocular infections is expected to be higher than that which could be assumed if it only had anti-bacterial activity.

[Combined Valvular Disease with Suspected Acquired von Willebrand Syndrome].

A 73-year-old female was referred to our department for surgical treatment of combined rheumatic valvular disease. She had undergone percutaneous transluminal mitral commissurotomy 29 years before. She underwent double valve replacement with bioprosthetic valves and tricuspid annuloplasty combined with left atrial appendectomy for chronic atrial fibrillation. Because of remarkable bleeding following surgery, rapid blood transfusion and re-thoracotomy were immediately performed. However, the bleeding persisted even after re-thoracotomy, and acquired von Willebrand syndrome due to valvular disease was suspected. Von Willebrand factor/factor Ⅷ preparation was administered, and bleeding promptly became under control. Recently, acquired von Willebrand syndrome due to valvular disease has attracted attention. We need to keep it in mind during perioperative management for patients with valvular disease.

Rupture of the Remaining Renal Artery Aneurysm While Waiting for Stage 2 Surgery for a Patient with Bilateral Renal Artery Aneurysms and Multiple Aneurysms.

A 21-year-old man was referred to our department for treatment of multiple aneurysms, including bilateral renal artery aneurysms. He was clinically diagnosed with Loeys-Dietz syndrome. So, we developed a 2-stage surgical strategy. The first surgery involved reconstructing the right renal artery and replacing part of the abdominal aorta, bilateral common iliac artery, and bilateral internal and external iliac arteries with a synthetic graft. Although stent grafting of the left renal artery aneurysm had been scheduled for the second surgery, sudden rupture of the left renal artery aneurysm forced us to perform emergency renal artery reconstruction.

Relationship between Blurring and Refocus Flip Angle in 3D-double Inversion Recovery MRI.

It is important to optimize imaging parameters in 3D-double inversion recovery (DIR) magnetic resonance imaging (MRI) for detecting cortical micro lesions. However, inadequate parameters markedly raise blurring in 3DDIR MRI. The purpose of this study was to evaluate the relationship between the blurring and refocus flip angle (RFA) in 3D-DIR MRI. White matter attenuated inversion recovery (WAIR) images as a test sample were obtained by 1.5T MRI with various RFA settings (30°, 40°, 60°, 100°, 140°, 180°, and variable refocus flip angle (VRFA)). Optimal RFA was evaluated using Scheffé's method (Nakaya changing method) by five observers. The results of average preferences indicated that RFA settings of under the 60° of RFA or VRFA suppressed the blurring in 3DDIR MRI. The yard sticks of RFAs of 30° and 40° were significantly higher than the yard sticks of other RFAs (p<0.01). For detecting cortical microlesions, it is very important to obtain WAIR images with no blurring. Using low RFA or VRFA didn't cause significant differences of signal intensity between high-frequency region and low-frequency region in k-space of 3D-DIR MRI. Therefore, it is recommended to set lower RFA (under 60° or VRFA) for suppressing blur in 3D-DIR MRI.

Inhibition by all-trans retinoic acid of collagen degradation mediated by corneal fibroblasts.

BACKGROUND: We examined the effect of all-trans retinoic acid on collagen degradation mediated by corneal fibroblasts. METHODS: Rabbit corneal fibroblasts were cultured with or without all-trans retinoic acid in a three-dimensional collagen gel, and the extent of collagen degradation was determined by measurement of hydroxyproline in acid hydrolysates of culture supernatants. Matrix metalloproteinase expression was examined by immunoblot analysis and gelatin zymography. The abundance and phosphorylation state of the endogenous nuclear factor-kappaB inhibitor IκB-α were examined by immunoblot analysis. Corneal ulceration was induced by injection of lipopolysaccharide into the central corneal stroma of rabbits and was assessed by observation with a slitlamp microscope. RESULTS: All-trans retinoic acid inhibited interleukin-1ß-induced collagen degradation by corneal fibroblasts in a concentration- and time-dependent manner. It also attenuated the release and activation of matrix metalloproteinases as well as the phosphorylation and degradation of IκB-α induced by interleukin-1ß in these cells. Topical application of all-trans retinoic acid suppressed corneal ulceration induced by injection of lipopolysaccharide into the corneal stroma. CONCLUSIONS: All-trans retinoic acid inhibited collagen degradation mediated by corneal fibroblasts exposed to interleukin-1ß, with this effect being accompanied by suppression of nuclear factor-kappaB signalling as well as of matrix metalloproteinase release and activation in these cells. All-trans retinoic acid also attenuated lipopolysaccharide-induced corneal ulceration in vivo. Our results therefore suggest that all-trans retinoic acid might prove effective for the treatment of patients with corneal ulceration.

[Transaortic Thoracic Endovascular Aortic Repair Via Right Anterior Mini-thoracotomy;Report of a Case].

An 81-year-old man presented with ruptured thoracic aortic aneurysm under stable condition. He had been suffering from chronic obstructive pulmonary disease, chronic renal failure and rheumatoid arthritis. We performed hybrid thoracic endovascular aortic repair via right anterior mini-thoracotomy inserting a device through a conduit on the ascending aorta. The patient was discharged without aorta-related complications.

Cyclic Triradicals Composed of Iminonitroxide-Gold(I) with Intramolecular Ferromagnetic Interactions.

A triangular gold(iminonitroxide-2-ide) trimer complex (5) was prepared and investigated to determine its magnetic properties. The results showed that the metalloid triradical is highly stable, even in solution under aerated conditions. The intramolecular exchange interaction of 5 was found to be positive (Jintra /kB ≈+29 K), thus showing that 5 is in a quartet ground state. In addition, a silver sandwich complex (5-Ag(+) -5) was prepared and its electronic and magnetic properties were also clarified.

Simultaneous inflammatory pseudotumors of the coronary arteries and abdominal aorta.

We herein report a rare case of cardiac and abdominal aortic inflammatory pseudotumors (IPTs). A 64-year-old male presented with a loss of appetite, abdominal distension and general fatigue. A cardiac tumor was suspected on the basis of computed tomography scans. A needle biopsy was performed, but it did not lead to a definitive diagnosis. At the same time, a 70-mm abdominal aortic aneurysm (AAA) was also detected. A full sternotomy was performed, and a huge, elastic hard tumor was found around the bilateral coronary arteries, anterior side of the right atria, ascending aorta and pulmonary artery. The pathological diagnosis was IPT, which was judged to be inoperable because of its anatomical location and the fact that the patient was a Jehovah's Witness, which precluded the administration of heterologous blood transfusions. The AAA was surgically treated, and the pathological diagnosis of the aneurysmal tissue also revealed IPT. Perioral steroid therapy was initiated, and the size of the tumor did not change for 1-2 years, but then gradually increased. The patient eventually died 8 years later, and the cause of his sudden death was considered to be heart failure caused by the pressure on the right atrium and ventricle due to the enlarged cardiac tumor.

Breaking the Limit of Cardiovascular Regenerative Medicine: Successful 6-Month Goat Implant in World's First Ascending Aortic Replacement Using Biotube Blood Vessels.

This study investigated six-month outcomes of first models of ascending aortic replacement. The molds used to produce the Biotube were implanted subcutaneously in goats. After 2-3 months, the molds were explanted to obtain the Biotubes (inner diameter, 12 mm; wall thickness, 1.5 mm). Next, we performed ascending aortic replacement using the Biotube in five allogenic goats. At 6 months, the animals underwent computed tomography (CT) and histologic evaluation. As a comparison, we performed similar surgeries using glutaraldehyde-fixed autologous pericardial rolls or pig-derived heterogenous Biotubes. At 6 months, CT revealed no aneurysmalization of the Biotube or pseudoaneurysm formation. The histologic evaluation showed development of endothelial cells, smooth muscle cells, and elastic fibers along the Biotube. In the autologous pericardium group, there was no evidence of new cell development, but there was calcification. The histologic changes observed in the heterologous Biotube group were similar to those in the allogenic Biotube group. However, there was inflammatory cell infiltration in some heterologous Biotubes. Based on the above, we could successfully create the world's first Biotube-based ascending aortic replacement models. The present results indicate that the Biotube may serve as a scaffold for aortic tissue regeneration.

A MAP1B-cortactin-Tks5 axis regulates TNBC invasion and tumorigenesis.

The microtubule-associated protein MAP1B has been implicated in axonal growth and brain development. We found that MAP1B is highly expressed in the most aggressive and deadliest breast cancer subtype, triple-negative breast cancer (TNBC), but not in other subtypes. Expression of MAP1B was found to be highly correlated with poor prognosis. Depletion of MAP1B in TNBC cells impairs cell migration and invasion concomitant with a defect in tumorigenesis. We found that MAP1B interacts with key components for invadopodia formation, cortactin, and Tks5, the latter of which is a PtdIns(3,4)P2-binding and scaffold protein that localizes to invadopodia. We also found that Tks5 associates with microtubules and supports the association between MAP1B and α-tubulin. In accordance with their interaction, depletion of MAP1B leads to Tks5 destabilization, leading to its degradation via the autophagic pathway. Collectively, these findings suggest that MAP1B is a convergence point of the cytoskeleton to promote malignancy in TNBC and thereby a potential diagnostic and therapeutic target for TNBC.

Low-flow perfusion technique for shaggy aortic arch.

BACKGROUND: The most common complication of thoracic aortic disease with shaggy aorta is cerebral infarction. We have performed "low-flow perfusion" as a method of extracorporeal circulation to prevent cerebral embolism in patients with strong atherosclerotic lesions in the aortic arch. METHODS: "Low-flow perfusion" is a method in which cardiopulmonary bypass is started by partial blood removal, approaching deep hypothermia while maintaining self-cardiac output. We compared the outcomes of 12 patients who underwent the "low-flow perfusion" method (Group L) with those of 12 who underwent normal extracorporeal circulation (Group N) during aortic arch surgery since 2019. RESULTS: Group L consisted of 8 males with an average age of 73 years old, and Group N consisted of 6 males with an average age of 73 years old. The average time from the start of cooling to ventricular fibrillation was 9.5 min in Group L and 3.6 min in Group N (p < 0.01). The eardrum temperature when ventricular fibrillation was reached was 28.2 °C in Group L and 32.5 °C in Group N (p = 0.01). A blood flow analysis also revealed low wall shear stress on the lesser curvature of the aortic arch. CONCLUSION: With this method, the intracranial temperature was sufficiently low at the time of ventricular fibrillation, and there was no need to increase the total pump flow. The low-flow perfusion method can prevent cerebral embolism by preventing atheroma destruction by the blood flow jet while maintaining the self-cardiac output during the cooling process.

Empagliflozin Suppresses the Differentiation/Maturation of Human Epicardial Preadipocytes and Improves Paracrine Secretome Profile.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce epicardial adipose tissue (EAT) in humans, enhancing cardioprotective effects on heart failure and atrial fibrillation. We investigated the direct effect of the SGLT2 inhibitor empagliflozin on human primary epicardial adipocytes and preadipocytes. SGLT2 is primarily expressed in human preadipocytes in the EAT. The expression levels of SGLT2 significantly diminished when the preadipocytes were terminally differentiated. Adipogenesis of preadipocytes was attenuated by empagliflozin treatment without affecting cell proliferation. The messenger RNA levels and secreted protein levels of interleukin 6 and monocyte chemoattractant protein 1 were significantly decreased in empagliflozin-treated adipocytes. Coculture of human induced pluripotent stem cell-derived atrial cardiomyocytes and adipocytes pretreated with or without empagliflozin revealed that empagliflozin significantly suppressed reactive oxygen species. IL6 messenger RNA expression in human EAT showed significant clinically relevant associations. Empagliflozin suppresses human epicardial preadipocyte differentiation/maturation, likely inhibiting epicardial adipogenesis and improving the paracrine secretome profile of EAT, particularly by regulating IL6 expression.

Potential efficacy of multipoint pacing in the reduction of mitral regurgitation volume: a case report.

A 70-year-old woman who had cardiac sarcoidosis and severe tethering mitral regurgitation (MR) and had been implanted with a biventricular pacemaker experienced recurrent hospitalisation due to decompensated heart failure (HF). Application of MultiPoint™ pacing reduced the MR volume and maintained the symptoms under control; however, the predicted longevity of the device significantly decreased because of the very high threshold of the added pacing site. Transcatheter mitral valve repair (TMVR) using MitraClip® was performed to further diminish the severe MR, thereby enabling the switch from highly consumptive multipoint pacing (MPP) to energy-saving single-point pacing. MPP could further reduce MR compared to the conventional single-point pacing, and this could be a bridging therapy to TMVR in some patients implanted with a biventricular pacemaker. This is the first case to report that switching from conventional single-point pacing to MPP decreased the MR, to some extent, resulting in the improvement of HF symptoms.

Endovascular aortic arch reconstruction using in situ stent-graft fenestration in the brachiocephalic artery.

A patient who had previously undergone retrosternal gastric tube reconstruction for esophageal cancer presented with an aortic arch aneurysm. The patient was treated with endovascular stent-graft placement without median sternotomy, followed by revascularization of the brachiocephalic trunk using percutaneous in situ graft fenestration. A 9-month follow-up examination revealed marked regression of the aneurysm with patency of the stent-graft, without any complications. This in situ fenestration technique may extend the limits of thoracic endovascular therapy for patients who are unsuitable for sternotomy or aortic side-clamping.