[Partial Arch Repair for Reruptured Aortic Arch Aneurysm due to Endoleak After 2-debranching Thoracic Endovascular Aortic Repair:Report of a Case].

A 67-year-old male was admitted to our hospital for sudden onset chest pain and hoarseness. He underwent 2-debranching thoracic endovascular aortic repair for a ruptured aortic arch aneurysm four years prior. However, computed tomography (CT) revealed an aneurysmal rerupture due to a typeⅠa endoleak. We performed partial arch replacement with uncovered stent removal under intermittent hypothermic circulatory arrest. We needed to be more careful than usual open heart surgery because a non-anatomical bypass procedure was performed. The surgery was successful without any major complications, and the patient was discharged on the 23th postoperative day. Reinterventions post-endovascular repair are sometimes difficult;thus, open surgery could be useful for arch replacement.

[Total Aortic Arch Replacement for Typeâ Endoleak after Thoracic Endovascular Aortic Repair using the Chimney Graft Technique:Report of a Case].

Here we report a case of total aortic arch replacement for typeⅠendoleak after thoracic endovascular aortic repair( TEVAR) using the concomitant chimney graft technique. An 81-year-old man was admitted with sudden back pain. Six years prior, he had undergone TEVAR for treatment of a distal aortic arch aneurysm. Preoperative computed tomography revealed an 80-mm-diameter arch aneurysm and typeⅠendoleak. The back pain was caused by impending aneurysmal rupture;therefore, urgent total arch replacement was performed. One stent was cut from the main endograft and anastomosed to its distal side. The bare metal stent in the left common carotid artery was removed and reconstructed at a healthy distal artery. Postoperative computed tomography revealed no endoleak of the aneurysm, and the patient's postoperative course was uneventful.

Bicuspidalization of the Native Tricuspid Aortic Valve: A Porcine in Vivo Model of Bicuspid Aortopathy.

Objective: To examine early histologic changes in the aorta exposed to bicuspid flow. Material and Methods: A porcine bicuspid aortopathy model was developed by suturing aortic cusps. Of nine pigs, eight underwent sham surgery (n=3) or bicuspidalization (n=5); one was used as an intact control. Wall shear stress (WSS) was assessed by computational fluid dynamics (CFD). Animals were exposed to normal or bicuspid flow for 48 h and were then euthanized for histologic examinations. Results: No animal died intraoperatively. One animal subjected to bicuspidalization died of respiratory failure during postoperative imaging studies. Echocardiography showed the aortic valve area decreased from 2.52±1.15 to 1.21±0.48 cm2 after bicuspidalization, CFD revealed increased maximum WSS (10.0±5.2 vs. 54.0±25.7 Pa; P=0.036) and percentage area of increased WSS (>5 Pa) in the ascending aorta (30.3%±24.1% vs. 81.3%±13.4%; P=0.015) after bicuspidalization. Hematoxylin-eosin staining and transmission electron microscopy showed subintimal edema and detached or degenerated endothelial cells following both sham surgery and bicuspidalization, regardless of WSS distribution. Conclusion: A bicuspid aortic valve appears to increase aortic WSS. The endothelial damage observed might have been related to non-pulsatile flow (cardiopulmonary bypass). Chronic experiments are needed to clarify the relationship between hemodynamic stress and development of bicuspid aortopathy.

IL-25 exacerbates autoimmune aortitis in IL-1 receptor antagonist-deficient mice.

IL-25, a member of the IL-17 family of cytokines, is known to enhance type 2 immune responses, but suppress type 3 (IL-17A)-mediated immune responses. Mice deficient in IL-1 receptor antagonist (Il1rn-/- mice) have excessive IL-1 signaling, resulting in spontaneous development of IL-1-, TNF- and IL-17A-dependent aortitis. We found that expression of II25 mRNA was increased in the aortae of Il1rn-/- mice, suggesting that IL-25 may suppress development of IL-1-, TNF- and IL-17A-dependent aortitis in Il1rn-/- mice by inhibiting type 3-mediated immune responses. However, we unexpectedly found that Il25-/-Il1rn-/- mice showed attenuated development of aortitis, accompanied by reduced accumulation of inflammatory cells such as dendritic cells, macrophages and neutrophils and reduced mRNA expression of Il17a and Tnfa-but not Il4 or Il13-in local lesions compared with Il1rn-/- mice. Tissue-, but not immune cell-, derived IL-25 was crucial for development of aortitis. IL-25 enhanced IL-1ß and TNF production by IL-25 receptor-expressing dendritic cells and macrophages, respectively, at inflammatory sites of aortae of Il1rn-/- mice, contributing to exacerbation of development of IL-1-, TNF- and IL-17A-dependent aortitis in those mice. Our findings suggest that neutralization of IL-25 may be a potential therapeutic target for aortitis.

IL-33, IL-25 and TSLP contribute to development of fungal-associated protease-induced innate-type airway inflammation.

Certain proteases derived from house dust mites and plants are considered to trigger initiation of allergic airway inflammation by disrupting tight junctions between epithelial cells. It is known that inhalation of proteases such as house dust mite-derived Der p1 and/or papaya-derived papain caused airway eosinophilia in naïve mice and even in Rag-deficient mice that lack acquired immune cells such as T, B and NKT cells. In contrast, little is known regarding the possible involvement of proteases derived from Aspergillus species (fungal-associated proteases; FAP), which are ubiquitous saprophytic fungi in the environment, in the development of allergic airway eosinophilia. Here, we found that inhalation of FAP by naïve mice led to airway eosinophilia that was dependent on protease-activated receptor-2 (PAR2), but not TLR2 and TLR4. Those findings suggest that the protease activity of FAP, but not endotoxins in FAP, are important in the setting. In addition, development of that eosinophilia was mediated by innate immune cells (ILCs) such as innate lymphoid cells, but not by acquired immune cells such as T, B and NKT cells. Whereas IL-33, IL-25 and thymic stromal lymphopoietin (TSLP) are involved in induction of FAP-induced ILC-mediated airway eosinophilia, IL-33-rather than IL-25 and/or TSLP-was critical for the eosinophilia in our model. Our findings improve our understanding of the molecular mechanisms involved in induction of airway inflammation by FAP.

The roles of IL-17C in T cell-dependent and -independent inflammatory diseases.

IL-17C, which is a member of the IL-17 family of cytokines, is preferentially produced by epithelial cells in the lung, skin and colon, suggesting that IL-17C may be involved in not only host defense but also inflammatory diseases in those tissues. In support of that, IL-17C was demonstrated to contribute to development of T cell-dependent imiquimod-induced psoriatic dermatitis and T cell-independent dextran sodium sulfate-induced acute colitis using mice deficient in IL-17C and/or IL-17RE, which is a component of the receptor for IL-17C. However, the roles of IL-17C in other inflammatory diseases remain poorly understood. Therefore, we investigated the contributions of IL-17C to development of certain disease models using Il17c-/- mice, which we newly generated. Those mice showed normal development of T cell-dependent inflammatory diseases such as FITC- and DNFB-induced contact dermatitis/contact hypersensitivity (CHS) and concanavalin A-induced hepatitis, and T cell-independent inflammatory diseases such as bleomycin-induced pulmonary fibrosis, papain-induced airway eosinophilia and LPS-induced airway neutrophilia. On the other hand, those mice were highly resistant to LPS-induced endotoxin shock, indicating that IL-17C is crucial for protection against that immunological reaction. Therefore, IL-17C neutralization may represent a novel therapeutic approach for sepsis, in addition to psoriasis and acute colitis.

IL-36α is involved in hapten-specific T-cell induction, but not local inflammation, during contact hypersensitivity.

Levels of IL36α are known to be increased in specimens from patients with atopic dermatitis and psoriasis. In addition, it has been reported that IL-36α is crucial for development of imiquimod-induced psoriatic dermatitis in mice. On the other hand, the role of IL-36α in induction of allergic contact dermatitis/contact hypersensitivity (ACD/CHS) is poorly understood. We found that IL-36α was produced in keratinocytes of mice during imiquimod-induced psoriatic dermatitis, but it was hardly detectable in the skin of mice during either fluorescein isothiocyanate (FITC)- or 1-fluoro-2, 4-dinitrobenzene (DNFB)-induced CHS. Although IL-36α can enhance activation of dendritic cells (DCs) and T cells, in CHS, IL-36α was not essential for DC migration from the skin to draining LNs, but it was required for induction or activation of hapten-specific T cells such as Th/Tc1 or Th17 cells. However, local inflammation, assessed by measurement of ear skin thickness, was comparable between wild-type and IL-36α-deficient mice during both FITC- and DNFB-induced CHS. These observations indicate that IL-36α is involved in induction and/or activation of hapten-specific T-cell subsets in the sensitization phase of CHS, but not essential for induction of local inflammation in the elicitation phase.

IL-31 is crucial for induction of pruritus, but not inflammation, in contact hypersensitivity.

IL-31, which is a member of the IL-6 family of cytokines, is produced mainly by activated CD4+ T cells, in particular activated Th2 cells, suggesting a contribution to development of type-2 immune responses. IL-31 was reported to be increased in specimens from patients with atopic dermatitis, and IL-31-transgenic mice develop atopic dermatitis-like skin inflammation, which is involved in the pathogenesis of atopic dermatitis. However, the role of IL-31 in development of contact dermatitis/contact hypersensitivity (CHS), which is mediated by hapten-specific T cells, including Th2 cells, is not fully understood. Therefore, we investigated this using IL-31-deficient (Il31-/-) mice, which we newly generated. We demonstrated that the mice showed normal migration and maturation of skin dendritic cells and induction of hapten-specific T cells in the sensitization phase of FITC-induced CHS, and normal induction of local inflammation in the elicitation phase of FITC- and DNFB-induced CHS. On the other hand, those mice showed reduced scratching frequency and duration during FITC- and/or DNFB-induced CHS. Our findings suggest that IL-31 is responsible for pruritus, but not induction of local skin inflammation, during CHS induced by FITC and DNFB.

IL-25 enhances TH17 cell-mediated contact dermatitis by promoting IL-1ß production by dermal dendritic cells.

BACKGROUND: In addition to thymic stromal lymphopoietin and IL-33, IL-25 is known to induce TH2 cytokine production by various cell types, including TH2 cells, TH9 cells, invariant natural killer T cells, and group 2 innate lymphoid cells, involved in TH2-type immune responses. Because both TH2-type and TH17-type cells/cytokines are crucial for contact hypersensitivity (CHS), IL-25 can contribute to this by enhancing TH2-type immune responses. However, the precise role of IL-25 in the pathogenesis of fluorescein isothiocyanate-induced CHS is poorly understood. OBJECTIVE: We investigated the contribution of IL-25 to CHS using Il25-/- mice. METHODS: CHS was evaluated by means of measurement of ear skin thickness in mice after fluorescein isothiocyanate painting. Skin dendritic cell (DC) migration, hapten-specific TH cell differentiation, and detection of IL-1ß-producing cells were determined by using flow cytometry, ELISA, and immunohistochemistry, respectively. RESULTS: In contrast to thymic stromal lymphopoietin, we found that IL-25 was not essential for skin DC migration or hapten-specific TH cell differentiation in the sensitization phase of CHS. Unexpectedly, mast cell- and non-immune cell-derived IL-25 was important for hapten-specific TH17 cell-mediated rather than TH2 cell-mediated inflammation in the elicitation phase of CHS by enhancing TH17-related, but not TH2-related, cytokines in the skin. In particular, IL-1ß produced by dermal DCs in response to IL-25 was crucial for hapten-specific TH17 cell activation, contributing to induction of local inflammation in the elicitation phase of CHS. CONCLUSION: Our results identify a novel IL-25 inflammatory pathway involved in induction of TH17 cell-mediated, but not TH2 cell-mediated, CHS. IL-25 neutralization can be a potential approach for treatment of CHS.

[Valve Replacement for Severe Aortic Stenosis in a Patient with Tangier Disease].

We report a case of severe aortic valve stenosis in a patient with Tangier disease. A 64-year-old female was diagnosed with Tangier disease on the basis of gene mutation. The serum levels of total cholesterol and high-density lipoprotein were 124 mg/dl and 4.3 mg/dl, respectively. She had a symptom of dyspnea and echocardiography revealed severe aortic valve stenosis with the maximum gradient of 60.5 mmHg. Chest computed tomography showed severe calcification of the ascending aorta and the aortic root. Aortic valve replacement using a bioprosthetic valve was performed. Several reports have been made on coronary artery revascularization in Tangier disease patients, but one on surgical treatment for aortic valve stenosis is extremely rare.

[Early Structural Valve Deterioration of Trifecta Biological Prosthesis;Report of a Case].

Trifecta valve is a 3rd-generation, stented bioprosthesis which is made from one bovine pericardial sheet. A 77-years-old male patient had undergone combine aortic valve replacement (AVR) using a 23-mm Trifecta valve and ascending aorta replacement for severe aortic valve regurgitation and ascending aorta aneurysm. The postoperative period was uneventful. However, he presented with dyspnea on effort and severe aortic valve regurgitation 31 months after operation. Re-do AVR with a new bioprosthetic valve was performed via 2nd sternotomy. Surgical inspection revealed that the Trifecta valve had a parastent tear in the left-coronary cusp without any calcification or vegetation. We report our experience with a case of early structural valve deterioration of Trifecta biological prosthesis and review relevant literatures.

Acute Aortic Dissection Occurring "Behind The Wheel", Report of 11 Cases.

We investigated the clinical picture of non-traumatic acute aortic dissection (AAD) occurring behind the wheel. Between 1990 and 2014, AAD had occurred in 11 patients while driving (nine men, mean age; 58.3 years, seven commercial drivers). The symptoms included chest and/or back pain (n = 9) and syncope (n = 2). One patient with syncope caused a traffic accident. Ten patients had type A dissection (DeBakey type I) and 1 type B dissection. In-hospital mortality was 9.9% (1/11). Our data showed if affected drivers are transported to a hospital in a timely fashion, a good surgical outcome can be expected.

Clinical outcomes and hemodynamics of the 19-mm Perimount Magna bioprosthesis in an aortic position: comparison with the 19-mm Medtronic Mosaic Ultra Valve.

BACKGROUND: When aortic valve replacement is performed in patients with a small aortic annulus, prosthesis-patient mismatch (PPM) is of concern because it can affect postoperative clinical outcomes. Although larger bioprosthetic valves have been well studied, the hemodynamics of 19-mm bioprostheses have been reported in only a small number of patients. The effectiveness as well as the impact of PPM on outcomes are thus still unclear. METHODS AND RESULTS: Postoperative clinical and hemodynamic variables were compared in 67 patients with a 19-mm Carpentier Edwards Perimount Magna bioprosthesis and in 10 patients with a 19-mm Medtronic Mosaic Ultra valve. Mean follow-up time was 13 months. There was no in-hospital mortality. Echocardiography 6.5±4.0 months after surgery showed significant decreases in the mean left ventricular (LV)-aortic pressure gradient, and decreases in the mean LV mass index. Reduction in LV mass index did not differ between the valve groups, despite a higher pressure gradient in the Mosaic group. Although PPM was detected in 21 patients in the Magna group, it did not affect regression of the LV mass index during the follow-up period. CONCLUSIONS: Use of the 19-mm Magna bioprosthesis appears to provide satisfactory clinical results. LV-aortic pressure gradient was lower in the Magna group. The present data suggest that PPM is not related to reduction in the LV mass index.