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Cytokine storm is recognized as one of the factors contributing to organ failures and mortality in patients with COVID-19. Due to chronic inflammation, COVID-19 patients with diabetes mellitus (DM) or renal disease (RD) have more severe symptoms and higher mortality. However, the factors that contribute to severe outcomes of COVID-19 patients with DM and RD have received little attention. In an effort to investigate potential treatments for COVID-19, recent research has focused on the immunomodulation functions of mesenchymal stem cells (MSCs). In this study, the correlation between DM and RD and the severity of COVID-19 was examined by a combined approach with a meta-analysis and experimental research. The results of a systematic review and meta-analysis suggested that the odd of mortality in patients with both DM and RD was increased in comparison to those with a single comorbidity. In addition, in the experimental research, the data showed that high glucose and uremic toxins contributed to the induction of cytokine storm in human lung adenocarcinoma epithelial cells (Calu-3 cells) in response to SARS-CoV Peptide Pools. Of note, the incorporation of Wharton's jelly MSC-derived extracellular vesicles (WJ-EVs) into SARS-CoV peptide-induced Calu-3 resulted in a significant decrease in nuclear NF-κB p65 and the downregulation of the cytokine storm under high concentrations of glucose and uremic toxins. This clearly suggests the potential for WJ-EVs to reduce cytokine storm reactions in patients with both chronic inflammation diseases and viral infection.

Triple-negative breast cancer (TNBC) is a highly aggressive and invasive type of breast cancer. In addition, type 2 diabetes mellitus (T2DM) is recognized as a risk factor for cancer metastasis, which is associated with mortality in patients with breast cancer. Cancer-associated fibroblasts (CAFs) generated from adipose tissue-derived mesenchymal stem cells (AT-MSCs) play a vital role in the progression of TNBC. However, to date, whether T2DM affects the ability of AT-MSCs to differentiate into CAFs is still unclear. In this study, we found that in coculture with TNBC cells [breast cancer cells (BCCs)] under hypoxic conditions, AT-MSCs derived from T2DM donors (dAT-MSCs) were facilitated to differentiate into CAFs, which showed fibroblastic morphology and the induced expression of fibroblastic markers, such as fibroblast activation protein, fibroblast-specific protein, and vimentin. This was involved in the higher expression of transforming growth factor beta receptor 2 (TGFβR2) and the phosphorylation of Smad2/3. Furthermore, T2DM affected the fate and functions of CAFs derived from dAT-MSCs. While CAFs derived from AT-MSCs of healthy donors (AT-CAFs) exhibited the markers of inflammatory CAFs, those derived from dAT-MSCs (dAT-CAFs) showed the markers of myofibroblastic CAFs. Of note, in comparison with AT-CAFs, dAT-CAFs showed a higher ability to induce the proliferation and in vivo metastasis of BCCs, which was involved in the activation of the transforming growth factor beta (TGFβ)-Smad2/3 signaling pathway. Collectively, our study suggests that T2DM contributes to metastasis of BCCs by inducing the myofibroblastic CAFs differentiation of dAT-MSCs. In addition, targeting the TGFβ-Smad2/3 signaling pathway in dAT-MSCs may be useful in cancer therapy for TNBC patients with T2DM.

Objective: Remodeling of the extracellular matrix plays a vital role in cardiovascular diseases. Using a mouse model of postnatal ascending aortic aneurysms (termed Fbln4 SMKO ), we have reported that abnormal mechanosensing led to aneurysm formation in Fbln4 SMKO with an upregulation of the mechanosensitive transcription factor, Egr1 (Early growth response 1). However, the role of Egr1 and its upstream regulator(s) in the initiation of aneurysm development and their relationship to an aneurysmal microenvironment are unknown. Approach and Results: To investigate the contribution of Egr1 in the aneurysm development, we deleted Egr1 in Fbln4 SMKO mice and generated double knockout mice ( DKO , Fbln4 SMKO ; Egr1 −/− ). Aneurysms were prevented in DKO mice (42.8%) and Fbln4 SMKO ; Egr1 +/− mice (26%). Ingenuity Pathway Analysis identified PAR1 (protease-activated receptor 1) as a potential Egr1 upstream gene. Protein and transcript levels of PAR1 were highly increased in Fbln4 SMKO aortas at postnatal day 1 before aneurysm formed, together with active thrombin and MMP (matrix metalloproteinase)-9, both of which serve as a PAR1 activator. Concordantly, protein levels of PAR1, Egr1, and thrombin were significantly increased in human thoracic aortic aneurysms. In vitro cyclic stretch assays (1.0 Hz, 20% strain, 8 hours) using mouse primary vascular smooth muscle cells induced marked expression of PAR1 and secretion of prothrombin in response to mechanical stretch. Thrombin was sufficient to induce Egr1 expression in a PAR1-dependent manner. Conclusions: We propose that thrombin, MMP-9, and mechanical stimuli in the Fbln4 SMKO aorta activate PAR1, leading to the upregulation of Egr1 and initiation of ascending aortic aneurysms.

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.

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.

Cancer metastasis is the leading cause of mortality among breast cancer patients. Type 2 diabetes mellitus (T2DM) has been suggested as a risk factor of breast cancer; however, whether or not T2DM is associated with breast tumor metastasis remains unclear. In this study, we examined the involvement of T2DM with breast cancer metastasis by a combined approach of a meta-analysis and experimental research. The results of a systematic review and meta-analysis suggested that diabetes significantly increases the risk of lymph node metastasis by 1.10-fold (

Two-dimensional perfusion angiography (2DPA) is utilized in hybrid operating rooms. 2DPA produces color map images and functional parameters to provide more robust visual and quantitative evaluations than conventional angiography. Its efficacy was suggested in five patients following bypass surgery; unexpected results were obtained in one patient, leading to a decision to perform surgical re-anastomosis. Furthermore, we found that the general anesthesia eliminates body movements that tend to disrupt 2DPA results. 2DPA was more useful during surgical revascularization than conventional angiography and provided more detailed information.

A 75-year-old woman presented at a prior hospital with persistent cough and was treated conservatively for a thrombosed-type aortic dissection (Stanford A). One-year after discharge, follow-up computerized tomography revealed a DeBakey type II, chronic dissecting aortic aneurysm enlarged to 54 mm. She was referred to our hospital with slight edema in the face and extremities and chest radiography showed calcification around the heart. Computerized tomography performed at the prior hospital showed a large spherical mass in the anterior pericardium in addition to the aortic dissection. We therefore resected the mass immediately before a total aortic arch replacement. Surgery was successful and uneventful with patient discharge on postoperative day 21. The final differential diagnosis was idiopathic, localized, constrictive pericarditis.

A 49-year-old man was transferred to our hospital by ambulance due to blunt chest trauma sustained in a car accident. Echocardiography and enhanced computed tomography showed hemopericardium without other vital organ damage. Emergent surgery was performed under strong suspicion of traumatic cardiac rupture. Careful inspection showed a rupture of the right upper pulmonary vein at the junction of the left atrium, a laceration of the inferior vena cava, and a left-side pericardium rupture, and they were repaired with running 4-0 polypropylene suture. Postoperative hemodynamics were stable. The patient was discharged ambulatory on postoperative day 15.

Rationale: Abnormal mechanosensing of smooth muscle cells (SMCs) resulting from the defective elastin-contractile units has been suggested to drive the formation of thoracic aortic aneurysms; however, the precise molecular mechanism has not been elucidated. Objective: The aim of this study was to identify the crucial mediator(s) involved in abnormal mechanosensing and propagation of biochemical signals during the aneurysm formation and to establish a basis for a novel therapeutic strategy. Methods and Results: We used a mouse model of postnatal ascending aortic aneurysms ( Fbln4 SMKO ; termed SMKO [SMC-specific knockout]), in which deletion of Fbln4 (fibulin-4) leads to disruption of the elastin-contractile units caused by a loss of elastic lamina-SMC connections. In this mouse, upregulation of Egr1 (early growth response 1) and angiotensin-converting enzyme leads to activation of Ang II (angiotensin II) signaling. Here, we showed that the matricellular protein, Thbs1 (thrombospondin-1), was highly upregulated in SMKO ascending aortas and in human thoracic aortic aneurysms. Thbs1 was induced by mechanical stretch and Ang II in SMCs, for which Egr1 was required, and reduction of Fbln4 sensitized the cells to these stimuli and led to higher expression of Egr1 and Thbs1. Deletion of Thbs1 in SMKO mice prevented the aneurysm formation in ≈80% of DKO (SMKO;Thbs1 knockout) animals and suppressed Ssh1 (slingshot-1) and cofilin dephosphorylation, leading to the formation of normal actin filaments. Furthermore, elastic lamina-SMC connections were restored in DKO aortas, and mechanical testing showed that structural and material properties of DKO aortas were markedly improved. Conclusions: Thbs1 is a critical component of mechanotransduction, as well as a modulator of elastic fiber organization. Maladaptive upregulation of Thbs1 results in disruption of elastin-contractile units and dysregulation of actin cytoskeletal remodeling, contributing to the development of ascending aortic aneurysms in vivo. Thbs1 may serve as a potential therapeutic target for treating thoracic aortic aneurysms.

Purpose There is less certainty regarding the best strategy for treating neonates with functional single ventricle (SV) and hypoplastic aortic arch. We have applied a modified extended aortic arch anastomosis (EAAA) and main pulmonary artery banding (PAB) as an initial palliation in neonates with transverse arch hypoplasia and assessed the mid-term outcomes. Methods In total, 10 neonates with functional SV and extensive hypoplasia or interruption of the arch underwent a modified EAAA (extended arch anastomosis with a subclavian flap) concomitant with main PAB through a thoracotomy without cardiopulmonary bypass. Patient age and weight ranged from 4 to 14 days and 2.3 to 3.8 kg, respectively. Results There were no hospital deaths although there were two late deaths. Gradients across the arch were 0 to 7 mmHg at postoperative day 1 and no arch reoperations were required. Two patients required balloon aortoplasty. Nine underwent bidirectional cavopulmonary shunt and two of them needed concomitant Damus-Kaye-Stansel (DKS) anastomosis. Six have completed Fontan. Conclusion Our modification of EAAA with main PAB for SV neonates may benefit a certain population with transverse arch hypoplasia as an option to be considered. Patients with the potential for developing outflow obstruction may be best managed with an initial DKS-type palliation.

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.

Pulmonary arterial hypertension (PAH) is a progressive disease which causes increased vascular resistance. In this study, our purpose was to quantify the micro-vascular remodeling in monocrotaline-induced PAH rats using synchrotron radiation pulmonary micro-angiography (SRPA), a method we have previously established in an in vivo rat model. To determine the relationship between endothelial function and vascular remodeling, the local expression of endothelin-1 (ET-1), endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF) was evaluated using immunohistochemical staining. Monocrotaline-induced PAH rats were created by subcutaneous injection of monocrotaline. After 2 weeks, SRPA was performed at the Photon Factory of the High Energy Accelerator Research Organization. The internal diameters of pulmonary arterioles were measured using SRPA images. Semi-quantified analyses of ET-1, eNOS and VEGF expression in pulmonary arterioles were performed by immunohistochemical staining. Micro-vascular density and the internal diameters of pulmonary arterioles were significantly decreased in PAH. ET-1 expression was significantly increased in PAH compared with the control (1.53 ± 0.45 vs. 0.80 ± 0.14) and eNOS expression was significantly decreased in PAH compared with the control (1.12 ± 0.59 vs. 1.91 ± 0.66), although VEGF expression did not differ between the groups. SRPA can be effectively used for visualizing the decreased pulmonary micro-vasculature associated with PAH. Increased ET-1 expression and decreased eNOS expression may contribute to the proliferation and vasospasm of pulmonary arterioles induced by endothelial dysfunction due to PAH. This SRPA technology may help to identify a correlation between endothelial function and micro-vasculature remodeling in PAH.

We measured the hydroxyl radical (.OH) generation in fourteen patients undergoing coronary artery bypass grafting (CABG), of whom seven patients underwent on-pump CABG with cardiopulmonary bypass (CPB) and seven patients underwent off-pump CABG without CPB. To detect .OH generation, we measured the urinary excretion of .OH products of creatinine (Cr), creatol (CTL; 5-hydroxycreatinine) and methylguanidine (MG) with HPLC using the one point sampling and collected urine during and after the operation. The urinary CTL value corrected urinary Cr value of on-pump CABG significantly increased about 3-5 times from the beginning of CPB to 4 h after operation compared to the baseline value before CPB in both the collected urine and the one point sampling urine. The urinary MG/Cr value in both groups did not change significantly. Significantly increased .OH generation was found during and soon after on-pump CABG.

Objectives: We studied the early outcome of bilateral internal thoracic artery T grafting.Methods: Coronary artery bypass grafting was studied retrospectively using bilateral internal thoracic artery T grafting in 51 patients. The T graft was made by anastomosing the free right internal thoracic artery to the in-situ left internal thoracic artery. Average patient age was 63.5±9.9 years, and the average number of anastomoses per patient was 3.6±0.9. In 35 patients, the right gastroepiploic artery (21 anastomoses in 20 patients), radial artery (1 anastomosis), free left internal thoracic artery (1 anastomosis) and saphenous vein graft (14 anastomoses in 13 patients) were used as additional bypass conduits.Results: Hospital mortality was 0%. The morbidity of stroke was 1.9% (1 patient) and deep sternal infection 0%. Patency of the in-situ left internal thoracic artery was 49/50 anastomoses (98%) and that of the free right internal thoracic artery 81/84 anastomoses (96.4%). Midterm coronary angiography in 7 patients demonstrated patent anastomosis of the T graft. Acute myocardial infarction unrelated to graft failure occurred in 2 patients during follow-up. Other patients were evaluated by exercise stress tests every year and none exhibited myocardial ischemia in the areas of T graft coronary revascularization. Three-year actuarial survival rate was 100% and freedom from cardiac events 96%.Conclusions: The bilateral internal thoracic artery T graft provides satisfactory early and midterm outcomes in properly selected patients.

We report a coil embolization-assisted thoracic endovascular aortic repair technique successfully applied to multiple saccular descending aortic aneurysms in a 74-year-old man. Because of the most distal aneurysm being located at the celiac trunk level and the distance between the superior mesenteric artery and the aneurysm being only 10 mm, a coil embolization of the distal saccular aneurysm was performed before stent delivery to secure a sufficient landing zone. Postoperative computed tomography showed an appropriate positioning of the endovascular devices without endoleak. This coil embolization-assisted technique may extend the indication of the endovascular aortic repair when a saccular aneurysm has an insufficient landing zone.

Five patients who had delayed stroke after cardiac surgery underwent intraarterial administration of a fibrinolytic agent for thromboembolism (n = 4) or thrombosis (n = 1) of the cerebral artery. Complete recanalization of the occluded artery was obtained in 3 patients and partial recanalization in 2. Additional angioplasty for basilar artery stenosis was performed in 1 patient. No patients exhibited rebleeding into the pericardial space or wound bleeding. All patients survived with moderate or full functional recovery. Immediate cerebral angiography and local thrombolysis may improve functional outcome and survival in patients with postcardiotomy cerebral thromboembolism.

患者は72歳男性.腰痛で発症.CTにて動脈硬化性腹部大動脈瘤にStanford B型急性大動脈解離が合併したものと診断された.腹部大動脈瘤は腎動脈下に存在し,動脈解離は左鎖骨下動脈起始部直下から右総腸骨動脈に及び,腹部分枝はすべて偽腔から分岐していた.胸部最大径4.8cm,腹部最大径6.5cmであった.多発腎梗塞を認め右腎は無機能であった.まず腹部大動脈瘤に対する人工血管置換術を発症3ヵ月で施行した.瘤壁は動脈硬化が強く解離の及んだ部位は脆弱で腰動脈からの出血のコントロールに難渋,バイタルサインの維持が困難となり,中枢側および末梢側を閉鎖し右腋窩-両大腿動脈バイパス術に術式変更となった.今回われわれは,大動脈解離が腹部大動脈瘤を越えて進展したまれな1例を経験したので報告した.

We report herein a case of subdural hematoma following aortic root and subtotal aortic arch replacement with selective cerebral perfusion in a 78-year-old woman. Her level of consciousness gradually deteriorated on postoperative day (POD) 2. Subdural hematoma, including fresh bleeding in bilateral frontal and parietal regions, was detected on brain computed tomography (CT) on POD 3. No head injury had been sustained previously. As the brain was not under pressure and disturbance of consciousness improved the next day, she was observed conservatively with follow-up brain CT. The subdural hematoma disappeared within about 2 months. The patient recovered completely and was discharged without sequelae.

Brainstem infarction associated with the primitive trigeminal artery is rare. We describe the case of a 61-year-old man with an acute myocardial infarction as well as a brainstem infarction. The patient was referred for coronary artery bypass grafting. Minimally invasive direct coronary artery bypass grafting (left internal thoracic artery to the second diagonal branch anastomosis) could be safely performed 10 weeks after an episode of brainstem infarction.

The implantation of a mechanical valve within the orifice of a mitral Duran flexible annular ring is presented. Exact orifice matches of the former ring and the new mechanical valve prosthesis (Advancing The Standard [ATS]; ATS Medical Inc, Minneapolis, MN) can be obtained using a standard mitral type ATS valve, when the size of the former Duran ring is larger than 31 mm. If ring dehiscence is not noted at reoperation after mitral valve repair, this procedure can be simply performed in patients with late mitral valve dysfunction requiring valve replacement.

Four cases of lower extremity hematoma in patients undergoing anticoagulant therapy after heart valve replacement are herein reported, with special emphasis on the comparative diagnostic value of ultrasonography and computerized tomography. Although conservative management is sufficient for patients with no neurological impairment, needle aspiration after autolysis of the hematoma, which can be confirmed by CT study, is also recommended.

The effects of low dose aprotinin (Trasylol) and preoperative administration of recombinant human erythropoietin (EPO) were evaluated in 144 patients undergoing cardiopulmonary bypass divided into four groups. Group I (n = 43) received a subcutaneous administration of EPO (18,000 U) one week before operation and intraoperative administration of low-dose aprotinin (mean; 1.38 +/- 0.26 x 10(6) kallikrein inactivator units; KIU) from extracorporeal circulation, group II (n = 39) received only preoperative administration of EPO, group III (n = 28) received only intraoperative administration of low-dose aprotinin (mean; 1.46 +/- 0.25 x 10(6) KIU), and group IV (n = 34) were not administered either drug. Compared with group IV, the intraoperative blood loss was significantly lower in group I (p < 0.01), and in group II or III (p < 0.05). The postoperative drainage in 24 hours was significantly lower in groups I and III receiving aprotinin than in the other groups. The mean volume of total homologous blood transfusion and the percentage of cases not requiring a homologous blood transfusion in each group was, respectively, 74 +/- 235 ml and 88.4% in group I, 282 +/- 1289 ml and 87.2% in group II, 414 +/- 584 ml and 60.7% in group III, and 976 +/- 1931 ml and 44.1% in group IV. Significant differences were recognized between group I and group IV (p < 0.05). These findings indicate that when used in combination, both drugs reduce blood loss and the need for a homologous blood transfusion more effectively than either drug alone.

graft prostheses has offered a largely successful alternative approach to the treatment of thoracic aortic aneurysm, an approach that is less invasive and carries a lower risk than does the standard operative method.1,2 However, cardiac surgeons who use the new method have not fully determined optimum indications for applying this alternative to open repair. We report on the autopsy of a patient with reruptured thoracoabdominal aneurysm after endovascular stent-grafting 6 months previously. Clinical summary. A 76-year-old man was admitted to our hospital with a diagnosis of thoracoabdominal aneurysm. He had undergone distal gastrectomy, a low anterior resection for early-stage gastric and sigmoid colon cancer, and radical neck resection for a soft-palate cancer. His height was 152 cm and his body weight was 39 kg. He had significant psychroesthesia in all 4 limbs and anterior chest pain. A large thoracoabdominal aneurysm, 10.0 × 6.7 cm in diameter, extended to just above the celiac artery. For the prevention of impending rupture, we decided that implantation of an endovascular stent-graft, rather than the usual thoracotomy and graft replacement, was indicated because of the patient’s poor general conditions. The dimensions of the stent-graft were determined by his preoperative computed tomographic and angiographic evaluations. The stent-graft, covered by 32 × 190-mm thin-walled woven polyester, was 34 mm in diameter and 200 mm long. Spinal fluid was drained through a catheter placed in the lumbar space before the operation to ensure spinal cord protection. The endovascular stent-graft was implanted into the descending thoracic aorta from the right femoral artery. Although we attempted to place and fix the distal edge of the stent-graft just above the celiac artery, it moved to the cranial side of the aorta. Because of perigraft leakage seen at the distal edge of the stent-graft on intraoperative angiogram, a second implantation was attempted. The second stent-graft, 35 ×