The inhibitory effect of DIF-3 on polyinosinic-polycytidylic acid-induced innate immunity activation in human cerebral microvascular endothelial cells.

For the treatment and prevention of autoinflammatory diseases, it is essential to develop the drug, regulating the innate immune system. Although differentiation-inducing factor (DIF) derivatives, extracted from the cellular slime mold, Dictyostelium discoideum, exhibit immunomodulatory effects, their effects on the regulation of innate immunity in brain are unknown. In this study, we used the human cerebral microvascular endothelial cell line, hCMEC/D3, to investigate the effects of DIF derivatives on the generation of C-X-C motif chemokine (CXCL) 10 and interferon (IFN)-ß induced by polyinosinic-polycytidylic acid (poly IC). DIF-3 (1-10 µM), but not DIF-1 and DIF-2, dose-dependently inhibited the biosynthesis of not only CXCL10 but also CXCL16 and C-C motif chemokine 2 induced by poly IC. DIF-3 also strongly decreased IFN-ß mRNA expression and protein release from the cells induced by poly IC through the prohibition of p65, a subtype of NF-ĸB, not interferon regulatory transcription factor 3 phosphorylation. In the docking simulation study, we confirmed that DIF-3 had a high affinity to p65. These results suggest that DIF-3 regulates the innate immune system by inhibiting TLR3/IFN-ß signaling axis through the NF-ĸB phosphorylation inhibition.

Postoperative cerebral infarction and arrhythmia after pulmonary lobectomy in Japan: a retrospective analysis of 77,060 cases in a national clinical database.

PURPOSE: To investigate the incidence of postoperative cerebral infarction after curative lobectomy, its association with the type of lobectomy, and how postoperative new-onset arrhythmia contributes to postoperative cerebral infarction. METHODS: The subjects of this analysis were 77,060 patients who underwent curative lobectomy for lung cancer between 2016 and 2018 according to the National Clinical Database. Incidences of postoperative cerebral infarction and postoperative new-onset arrhythmia were analyzed. Moreover, mediation analysis was performed to evaluate the causal pathway between postoperative new-onset arrhythmia and postoperative cerebral infarction. RESULTS: Postoperative cerebral infarction occurred in 110 (0.7%) patients after left upper lobectomy and in 85 (0.7%) patients after left lower lobectomy. Left upper lobectomy and left lower lobectomy were associated with a higher likelihood of postoperative cerebral infarction than right lower lobectomy. Left upper lobectomy was the strongest independent predictor of postoperative new-onset arrhythmia. However, in the mediation analysis, the odds ratio for cerebral infarction did not change after the addition of the factor of postoperative new-onset arrhythmia. CONCLUSION: Cerebral infarction occurred significantly more often not only after left upper lobectomy, but also after left lower lobectomy. Postoperative new-onset arrhythmia was less likely to be related to cerebral infarction after left upper lobectomy.

[Surgical Thrombectomy for Acute Massive Pulmonary Thromboembolism Induced by Giant Adenomyosis Uteri:Report of a Case].

A 52-year-old woman had giant adenomyosis uteri treated by pseudo-menopause therapy. However, she did not take oral anticoagulant for deep vein thrombosis prevention because of metrorrhagia. She developed pulmonary thromboembolism, and was refered to our department. She complained mild dyspnea but free from leg edema. Enhanced computed tomography (CT) showed massive thrombi in the central pulmonary artery trunk. Therefore, she underwent emergency thrombectomy. Three days later, uterine artery embolization( UAE) was performed to control metrorrhagia worsened by anticoagulation therapy. However, UAE caused significant swelling of the uterus, and bi-lateral external iliac veins were more compressed. Two months later, total hysterectomy was performed to prevent recurrence of pulmonary thromboembolism( PTE). Clinical course thereafter was satisfactory.

Amplatzer Vascular Plug With Endologix AFX Lining for Visceral Re-Entry Closure in a Patient With Chronic Type B Aortic Dissection.

PURPOSE: To demonstrate the efficacy of a combination of Amplatzer vascular plug (AVP2) and Endologix AFX for a visceral entry closure. CASE REPORT: A 70-year-old woman with treated chronic type B aortic dissection was seen to have sac enlargement. An isolated residual tear was observed at the origin of the celiac artery. A 12 mm AVP2 was successfully deployed for the entry closure. Angiography after the plug deployment still demonstrated residual flow to the false lumen. Hence, an Endologix AFX VELA proximal endograft was deployed, covering the AVP membrane and leaving no endoleak. CONCLUSION: Deployment of a vascular plug with Endologix AFX lining was efficacious for securing complete closure of an entry tear at the origin of the celiac artery in our patient. CLINICAL IMPACT: Vascular plugs are reported to be effective for closing small entries, although their effectiveness is limited when the entry site is not located on the flat intima, or in a high-flow situation. In the presented case, an isolated entry tear at the origin of the celiac artery was successfully closed with a vascular plug following Endologix AFX stent-graft lining of the true lumen.

Elucidation of the inhibitory effect of (+)-hopeaphenol on polyinosinic-polycytidylic acid-induced innate immunity activation in human cerebral microvascular endothelial cells.

Drug development for regulating the innate immune system is important for the prevention and treatment of autoinflammatory and autoimmune diseases. In this context, we investigated the effect of resveratrol derivatives on the inflammatory reactions in the brain. Resveratrol, which can be found in Vitis plants in the form of oligomers, exhibits neuroprotective effects; however, its regulatory effects on innate immunity are still unclear. We examined the effects of (+)-hopeaphenol, a resveratrol tetramer, and its derivatives on the polyinosinic-polycytidylic acid (poly IC)-induced production of interferon (IFN)-ß and C-X-C motif chemokine 10 (CXCL10) in the cultured human cerebral microvascular endothelial cell line hCMEC/D3. (+)-Hopeaphenol (1-10 µM) inhibited the poly IC-induced production of not only CXCL10 but also retinoic acid-inducible gene-I in a dose-dependent manner and significantly reduced the poly IC-induced IFN-ß gene expression and protein release from hCMEC/D3 cells by inhibiting the phosphorylation of p65 but not that of the interferon regulatory transcription factor IRF3. A docking study indicated a high affinity of (+)-hopeaphenol for p65. These results suggest that (+)-hopeaphenol can regulate the innate immune system by inhibiting the poly IC/IFN-ß/CXCL10 signaling axis via suppression of the phosphorylation of the transcription factor NF-ĸB.

Concomitant surgery for double-chambered right ventricle and coronary stenosis.

BACKGROUND AND AIMS: The clinical data of coronary artery disease in patients with double-chambered right ventricle are limited. We report an adult double-chambered right ventricle case with three-vessel coronary artery disease that was successfully treated with concomitant double-chambered right ventricle repair and coronary artery bypass grafting. MATERIALS AND METHODS: The patient case data was extracted from hospital records. RESULTS: The patient was the case of a 60-year-old man with a double-chambered right ventricle and three-vessel coronary artery disease. He underwent concomitant surgery comprising double-chambered right ventricle repair and coronary artery bypass grafting. Achieving cardiac arrest allowed us to obtain a good surgical view of the heavy and severely hypertrophied heart. Postoperative computed tomography revealed a feasible running course of the sequential graft, indicating that the path of the sequential graft should be clockwise (aorto-right coronary-left circumflex artery) in this unusual anatomical condition. DISCUSSION AND CONCLUSION: We report this rare disease combination and highlight the need for careful preoperative planning in such cases.

Extended aortic arch repair via simple median sternotomy using a parabronchial approach: A case report.

BACKGROUND AND AIMS: Surgery for extensive thoracic aortic aneurysms is challenging. We aim to report our novel extended arch repair method, which we termed "parabronchial approach" for such disease. MATERIALS AND METHODS: The patient case data was extracted from hospital records. RESULTS: The patient was the case of a 31-year-old woman with Takayasu's arteritis who developed aortic dissection. She underwent extended arch repair via a simple sternotomy approach. The left pulmonary artery compression with a retractor arrowed us to obtain adequate working space. Postoperative computed tomography revealed a distal anastomosis site level was at the sixth thoracic vertebra. DISCUSSION AND CONCLUSION: This parabronchial approach could reduce the frequency of choosing a highly invasive approach and can be a potential minimally invasive approach in cases requiring extensive thoracic aortic aneurysm repair.

Directing a dispersion cannula tip toward the aortic root during thoracic aortic arch surgery does not adversely affect cardiac function.

INTRODUCTION: Neurologic complications of open thoracic aortic surgery are devastating problems in patients with severely diseased aortas. This study aimed to clarify whether directing the aortic cannula tip toward the aortic root affects the postoperative cardiac function in patients undergoing open thoracic aortic surgery. METHODS: A total of 16 patients who underwent total or partial arch replacement between January 2014 and April 2019 were enrolled and divided into two groups. Ascending aorta perfusion was performed by placing the cannula tip toward the aortic root (reversed direction group, seven patients) or toward the aortic arch (standard direction group, nine patients). Intraoperative and perioperative data, including mortality, morbidity, and postoperative cardiac function, were compared between the groups. RESULTS: There were no hospital deaths or stroke events in either group. The aortic cross-clamping time was 102.4 ± 20.3 minutes in the reversed direction group and 87.1 ± 9.9 minutes in the standard direction group (p = 0.049). Furthermore, the intubation time was 28.4 ± 12.9 hours in the reversed direction group and 12.4 ± 6.8 hours in the standard direction group (p = 0.022). Both times were significantly longer in the reverse direction group. Postoperative serum creatine kinase-MB levels were significantly lower in the reversed direction group (6.2 ± 3.3 U/L vs 13.3 ± 4.8 U/L, respectively, p = 0.006). The cardiac output and cardiac index did not significantly differ. CONCLUSIONS: Directing the aortic cannula tip toward the aortic root does not adversely affect the postoperative cardiac function after aortic arch surgery.

Flow analysis during mock circulation in normal and aortic arch aneurysm models through an aortic cannula toward the aortic arch and root.

The aim of this study was to elucidate flow patterns of two different types of aortic cannulas inserted from the ascending aorta toward the aortic arch and root by mock circulation in a normal aortic arch and an aortic arch aneurysm model. Extracorporeal circulation was established using a centrifugal pump, a transparent glass normal aortic arch model, and an aortic arch aneurysm model for measurement by particle image velocimetry. The Stealthflow and Dispersion cannulas were used to elucidate the characteristics of the flow pattern and velocity under the condition of the cannula tip toward the aortic arch and aortic root. In the normal aortic arch model, high-velocity exit flow ranging from 0.7 to 0.8 m/s was detected in the proximal aortic arch by directing the cannula tip toward the aortic arch, whereas flow velocity in the aortic arch was < 0.2 m/s by directing the cannula tip toward the aortic root. In the aortic arch aneurysm model, high-velocity exit flow ranging from 0.5 to 0.8 m/s was detected in the aortic arch by directing the cannula tip toward the aortic arch, whereas flow velocity in the aortic arch was decreased to less than 0.2 m/s by directing the cannula tip toward the aortic root. Directing the aortic cannula tip toward the aortic root allowed the high-velocity exit flow to attenuate in velocity, so that flow velocity in the aortic arch was sufficiently reduced by reversed flow and vortex formation in both the normal and aortic arch aneurysm models.

The utility of extracorporeal membrane oxygenation in patients with circulatory collapse by electrical storm.

In patients experiencing electrical storm, intensive care using extracorporeal membrane oxygenation (ECMO) is an efficient treatment to overcome a hemodynamically unstable condition. The aim of this study was to examine the utility of ECMO in patients with circulatory collapse by electrical storm. We retrospectively examined 17 consecutive patients receiving veno-arterial ECMO for electrical storm between January 2016 and December 2018 in our institution. We compared survivors (n = 11) and non-survivors (n = 6). Thirteen were weaned from ECMO, of whom 11 patients (64.7%) survived and were discharged from hospital, while 6 patients died (35.3%). In comparisons between survivors and non-survivors, blood pH before starting ECMO was significantly higher in survivors (pH 7.32) than in non-survivors (pH 6.89, p = 0.027). Blood lactate level was significantly lower in survivors (6.2 mmol/L) than in non-survivors (12.2 mmol/L, p = 0.044). Complications of hypoxic ischemic encephalopathy were found in 4 non-survivors (66.7%), compared to survivors (0%, p = 0.006). Durations of intensive care unit stay and hospital stay were significantly longer in survivors (271 h, 62 days) than in non-survivors (50 h, 3 days, respectively). Outcomes of treatment using ECMO in patients with circulatory collapse due to electrical storm proved satisfactory. Increases in blood lactate level and decreases in blood pH before starting ECMO were thought to be related to mortality due to suspected irreversible organ damage by hypoxia before ECMO.

Aortic root and total arch replacement in a patient with prior ascending aortic repair for type-A aortic dissection.

A 63-year-old man was admitted to our hospital owing to the shortness of breath. He had undergone ascending aortic repair for acute type-A aortic dissection 14 years ago. In the previous surgery, the primary entry of the ascending aorta had been resected using direct end-to-end anastomosis after transecting the ascending aorta at the level of the entry and gluing the false lumen using a gelatin-resorcin-formalin glue. The anastomosis site on the ascending aorta had been reinforced using Teflon felt strips. The patient developed heart failure owing to severe aortic regurgitation caused by aortic root dilatation. Since the aortic arch was also dilated, he underwent aortic arch and root replacement. The distinctive difficulties experienced during surgery owing to the prior ascending aortic direct repair have been highlighted in this report.

Coronary artery bypass grafting after sternal turnover procedure and a review of the literature.

We report a case of complete revascularization after a sternal turnover procedure through median sternotomy in a patient with multivessel coronary artery disease. The patient had unusual anatomical features, such as the anterior protrusion of the middle-to-distal sternum and absent bilateral internal thoracic arteries (ITAs). The single-blade sternum retractor and the Omni-Tract retractors are simple and reliable tools for lifting and widening the thoracic wall around the xiphoid process. The bilateral radial arteries and the great saphenous vein were used as bypass grafts. Computed tomography was used to visualize the sternum supplied by the superior epigastric arteries (SEAs); presurgical abdominal ultrasonography revealed the course and crossing point of the developed SEAs. Since ITAs were absent, we preserved the SEAs to prevent sternal ischemia. No sternal complications or graft occlusion were observed during follow-up.

Urgent repair of postinfarct ventricular septal rupture with ECPELLA support: A case report.

A 74-year-old woman developed inferior myocardial infarction due to right coronary artery occlusion and underwent percutaneous coronary intervention. Two days later, echocardiography revealed ventricular septal rupture, and Impella CP was inserted to avoid emergency surgery. However, the patient's hemodynamics deteriorated rapidly, necessitating additional venoarterial extracorporeal membranous oxygenation support with concomitant Impella support (ECPELLA). The ventricular septal rupture was surgically repaired using the extended sandwich technique via a right ventricular approach; the ascending aorta was clamped with the clampable portion of the Impella. The patient was successfully weaned from the Impella 3 days postsurgery. This case suggests that urgent surgery with ECPELLA support could be a useful option for patients with ventricular septal rupture, even in severe cases wherein emergency surgery is unavoidable.

Coronary artery bypass for Takayasu's arteritis involving the aortic root in a child.

The patient was a 12-year-old female who presented with angina pectoris, aortic root dilatation, and aortic regurgitation (AR) caused by Takayasu's arteritis (TA). After the management of systemic inflammation, she underwent off-pump coronary artery bypass with the radial artery (RA), which extended from the left axillary artery to the left descending coronary artery, via left mini-thoracotomy. Postoperative angiography revealed the growth of the RA graft. The patient is well 4 years after surgery without progression of AR. Off-pump coronary artery bypass is a palliative therapy. Moreover, it could be a feasible option in a child with TA involving the aortic root.

Clinical evaluation of a new dispersive aortic cannula.

INTRODUCTION: Cerebral injury is a serious complication in open-heart surgery. Once it occurs, it causes significant disability and death. We developed a novel dispersive aortic cannula named the Stealth Flow cannula and used it as a standard aortic cannula in cardiopulmonary bypass. The aim of this study was to evaluate the efficiency of this aortic cannula. METHODS: A total of 182 consecutive patients undergoing cardiac surgery using cardiopulmonary bypass were studied. The patients were divided into two groups: the Soft-Flow cannula group (n = 89) and the Stealth Flow cannula group (n = 93). Patients with a shaggy aortic arch were excluded from this study because the cannulae were inserted at the ascending aorta with a cannula tip directed toward the aortic root in these cases. Patients with multiple arterial perfusion sites were also excluded. Complications including early mortality, perioperative stroke, and intraoperative aortic injury were compared between the two groups. RESULTS: Age, operative procedure, cardiopulmonary bypass time, and the Japan SCORE were not significantly different between the groups. In comparisons between the Stealth Flow and Soft-Flow groups, the incidences of early mortality, perioperative stroke, intraoperative aortic dissection, and all complications were 1.08% versus 1.12% (p = 0.98), 1.1% versus 2.2% (p = 0.53), 0% versus 1.1% (p = 0.33), and 1.1% versus 3.4% (p = 0.29), respectively. The incidence of major cardiovascular events, including early death, perioperative stroke, and aortic dissection, was not different. CONCLUSIONS: The Stealth Flow cannula, which was designed based on our previous experimental study, contributed to reducing cerebral and aortic events as much as the Soft-Flow cannula in the present clinical study.

[Aortic Root Partial Reconstruction Combined with Intraoperative Aortic Dissection:Report of a Case].

A 73-year-old woman with Valsalva aneurysm and mitral regurgitation was introduced to our department. We performed combined operation including aortic root partial repair and mitral valve repair. After wenning from cardiopulmonary bypass, intraoperative aortic dissection was confirmed by transesophageal echocardiography from the ascending aorta to the descending aorta, entry was near to proximal anastomosis line of the ascending aorta. To avoid heart failure, the ascending aorta wrapping by prothesis graft was performed to protect from urgent rupture postoperative at first stage. According to contrast computed tomography (CT) findings, location of entry was correspond with aortic clamping. We performed partial aortic replacement including innominate artery reconstruction for her at fourth day postoperative for treating aortic dissection at second stage. Postoperative course was uneventful.

[Re-operation for Recurrent Constrictive Pericarditis with Multiple Organ Dysfunction].

The patient was a 64-year-old man with recurrent constrictive pericarditis which developed 12 years after the initial pericardiectomy. He had bilateral heart failure with severe left ventricular diastolic dysfunction, massive ascites, renal failure, and coagulopathy. Computed tomography showed a heavily calcified pericardium around the right atrium, the phrenic side of the right ventricle, and the left ventricle. He underwent pericardiectomy via median sternal re-entry. The calcified pericardium was safely decorticated with an ultrasonic surgical knife. The pericardium around the left ventricular side was safely decorticated under cardiopulmonary bypass and use of a heart positioner. Although permanent hemodialysis was necessary after the operation, he has been well for 6 years since the operation.

Outcomes of Pulmonary Embolectomy for Acute Pulmonary Embolism.

BACKGROUND: Acute pulmonary embolism (PE) is a major threat to the health and lives of hospitalized patients. This study was conducted to clarify the real-world outcomes of pulmonary embolectomy.Methods and Results:Retrospective investigation of 355 patients who underwent pulmonary embolectomy for acute PE was conducted using the Japanese Cardiovascular Surgery Database. Risk factors for operative death within 30 days after pulmonary embolectomy and major adverse cardiovascular events (MACE), including operative death, postoperative stroke and postoperative coma, were analyzed. Cardiopulmonary resuscitation (CPR) was required preoperatively in 27.6%, and preoperative veno-arterial extracorporeal membrane oxygenation was performed in 26.5%. Urgent or emergency operation was performed in 93% of patients. Operative mortality rate was 73/355 (20.6%). Incidence of MACE was 97/355 (27.3%). In univariate analysis, preoperative predictors of death were obesity, renal dysfunction, chronic obstructive pulmonary disease, liver injury, recent myocardial infarction, shock, refractory shock, CPR, heart failure, inotrope use, poor left ventricular function, preoperative arrhythmia and tricuspid regurgitation. In multivariate analysis, independent risk factors for operative death were heart failure (P=0.013), poor left ventricular function (P=0.007), and respiratory failure (P=0.001). Poor left ventricular function (P=0.033), preoperative CPR (P=0.002) and respiratory failure (P=0.007) were independent risk factors for MACE. CONCLUSIONS: The outcomes of pulmonary embolectomy were acceptable, considering the urgency and preoperative comorbidities of patients. Early triage of patients with hemodynamically unstable PE is important.

Effect of inflow cannula side-hole number on drainage flow characteristics: flow dynamic analysis using numerical simulation.

BACKGROUND: Venous drainage in cardiopulmonary bypass is a very important factor for safe cardiac surgery. However, the ideal shape of venous drainage cannula has not been determined. In the present study, we evaluated the effect of side-hole number under fixed total area and venous drainage flow to elucidate the effect of increasing the side-hole numbers. METHOD: Computed simulation of venous drainage was performed. Cannulas were divided into six models: an end-hole model (EH) and models containing four (4SH), six (6SH), eight (8SH), 10 (10SH) or 12 side-holes (12SH). Total orifice area of the side-holes was fixed to 120 mm2 on each side-hole cannula. The end-hole orifice area was 36.3 mm2. The total area of the side-holes was kept constant when the number of side-holes was increased. RESULT: The mean venous drainage flow rate of the EH, 4SH, 6SH, 8SH, 10SH and 12SH was 2.57, 2.52, 2.51, 2.50, 2.49, 2.41 L/min, respectively. The mean flow rate decreased in accordance with the increased number of side-holes. CONCLUSION: We speculate that flow separation at the most proximal site of the side-hole induces stagnation of flow and induces energy loss. This flow separation may hamper the main stream from the end-hole inlet, which is most effective with low shear stress. The EH cannula was associated with the best flow rate and flow profile. However, by increasing side-hole numbers, flow separation occurs on each side-hole, resulting in more energy loss than the EH cannula and flow rate reduction.