Successful treatment of chronic type B aortic dissection complicated by disseminated intravascular coagulopathy with recombinant human soluble thrombomodulin after thoracic endovascular aortic repair.

OBJECTIVES: We report a case of successful thoracic endovascular aortic repair (TEVAR) of chronic type B aortic dissection complicated by disseminated intravascular coagulopathy. METHODS: The patient suffered from chronic type B aortic dissection coexisting with a large false lumen and an intimal tear. He underwent TEVAR with left common carotid-left subclavian artery bypass. RESULTS: The following day, the patient exhibited a bleeding tendency and marked subcutaneous hemorrhage. He had a low fibrinogen level, a low platelet count, and high levels of fibrin dimer product and D-dimer. We diagnosed the condition as disseminated intravascular coagulopathy and administered recombinant human soluble thrombomodulin (rhTM). The patient recovered successfully from disseminated intravascular coagulopathy and was discharged on postoperative day 6. CONCLUSIONS: We successfully treated a patient with chronic type B aortic dissection with a large intimal tear complicated by postoperative disseminated intravascular coagulopathy using TEVAR followed by rhTM administration. rhTM may be considered in patients with large intimal tear and false lumen.

Left ventricular free wall perforation by a right ventricular pacemaker lead: a case report.

BACKGROUND: Lead perforation is one of the major complications of pacemaker implantation, but cases of right ventricular (RV) lead perforation through the septum and left ventricle are rarely reported. We described a rare case of left ventricular (LV) free wall perforation by an RV lead and the management of this complication. CASE SUMMARY: An 84-year-old man was admitted with a dual-chamber pacemaker due to pacing failure caused by an RV lead fracture. New lead implantation was performed on the next day, but pacing failure occurred again on the second post-operative day (POD). We found the lead perforation on the fluoroscopy during temporary pacemaker insertion. Computed tomography scan and transthoracic echocardiogram showed that the added lead perforated through both the septum and LV free wall. A new lead was inserted on the fourth POD, and an off-pump open chest surgery for extraction of the penetrating lead was performed uneventfully on the 20th POD. DISCUSSION: We considered that some features of the lead (SelectSecure 3830-69, Medtronic) may be related to this complication, as the lead was very thin, had a non-retractable bare screw and was inserted with a dedicated delivery catheter. We have to be careful when performing implantation of this kind of lead to avoid such a rare complication.

Extended thoracic endovascular aortic repair for residual aortic dissection after type A aortic dissection repair.

OBJECTIVE: We investigated the outcomes of extended coverage of the descending thoracic aorta by thoracic endovascular aortic repair (TEVAR) for residual chronic type B aortic dissection after type A aortic dissection (TAAD) repair. METHODS: From November 2015 to August 2020, 36 patients underwent extended TEVAR for residual intimal tear after TAAD repair. We specifically investigated the methods and outcomes of this procedure. RESULTS: TEVAR consisted of isolated TEVARs (n = 29), single-vessel debranching TEVAR (6), and two-vessel debranching TEVAR (1). The mean time from TAAD repair to TEVAR was 27 ± 33 months (2-86 months). The TEVAR devices used were Valiant (28 cases), GORETAG (4), Relay plus (2), and TX2 (2). Technical success of TEVAR was 100%. The distal ends of the stent grafts were T 8 (1 case), T 9 (5), T 10 (6), T 11 (9), and T 12 (15), with an average of T 11 ± 1. The average length of hospital stay after TEVAR was 9 ± 3 days (5-17 days). There were no surgical/hospital deaths or complications. The average postoperative follow-up period was 21 ± 15 months without death or reintervention. CONCLUSIONS: The short-term outcomes of extended TEVAR for residual chronic type B aortic dissection after TAAD repair were acceptable without perioperative SCI. Aggressive descending thoracic aorta coverage may prevent aortic events, and extended TEVAR may be a preemptive treatment for the downstream aorta. Mid- to long-term results should be clarified.

5-hydroxymethyl-2-furaldehyde purified from Japanese pear (Pyrus pyrifolia Nakai cv. Nijisseiki) juice concentrate inhibits melanogenesis in B16 mouse melanoma cells.

Pear juice concentrate prepared by boiling Japanese pear (Pyrus pyrifolia Nakai cv. Nijisseiki) juice can significantly inhibit the activity of tyrosinase, a key enzyme in melanin synthesis in human skin. Using the ethanol extract of pear juice concentrate, we homogeneously purified an active compound that was identified as 5-hydroxymethyl-2-furaldehyde (5-HMF) through 1H- and 13C-NMR and mass spectroscopy. We observed that 5-HMF inhibited the monophenolase and diphenolase activities of mushroom tyrosinase as a mixed-type inhibitor (K i values of 3.81 and 3.70 mmol/L, respectively). In B16 mouse melanoma cells, treatment with 170 µmol/L of 5-HMF significantly reduced α-melanocyte-stimulated melanin synthesis by suppressing the cyclic adenosine monophosphate-dependent signaling pathway involved in melanogenesis. The results of our study indicated that 5-HMF can be potentially used as a skin-lightening agent in the cosmetic industry. Abbreviations: AC: adenylate cyclase; CREB: cAMP response element-binding protein; dhFAME: S-(-)-10,11-Dihydroxyfarnesoic acid methyl ester; DMEM: dulbecco's modified eagle medium; l-DOPA: 3-(3,4-Dihydroxyphenyl)- l-alanine; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; HEPES: 4-(2-Hydroxyethyl)-1-piperazine ethane sulfonic acid; 5-HMF: 5-Hydroxymethyl-2-furaldehyde; MITF: microphthalmia-associated transcription factor; α-MSH: α-Melanocyte-stimulating hormone; PKA: protein kinase A; PVDF: polyvinylidene difluoride; SDS: sodium dodecyl sulfate; TRP1: tyrosinase-related protein 1; TRP2: tyrosinase-related protein 2.

Dimethyl fumarate suppresses metastasis and growth of melanoma cells by inhibiting the nuclear translocation of NF-κB.

BACKGROUND: Malignant melanoma is among the deadliest forms of skin cancers, and its incidence has been increasing over the past decades. In malignant melanoma, activation of the nuclear factor kappa B (NF-κB) promotes survival, migration, and invasion of cancer cells. Anti-NF-κB agents for treating metastatic melanoma would be beneficial, but no such drug is approved as either monotherapy or adjuvant therapy. Dimethyl fumarate (DMF) is an approved anti-inflammatory drug already in clinical use for psoriasis and multiple sclerosis. OBJECTIVE: We investigated the anti-tumour effect of DMF treatment in metastatic melanoma in vitro and in vivo. METHODS: The cell viability was assessed via trypan blue exclusion assay. The migration and invasion was analyzed in a Boyden chamber assay. The anti-metastatic effects and anti-tumour activity of DMF was determined in an in-vivo model. The expressions of NF-κB pathway and NF-κB regulatory proteins were detected via western blotting. RESULTS: DMF decreased the cell viability, migration and invasion in vitro. In addition, DMF inhibited spontaneous metastasis and tumour growth. Mechanistically, DMF prevented the nuclear translocation of NF-κB, whereas no changes were observed in the phosphorylation levels of inhibitor of kappa B (IκB). In addition, DMF inhibited the expression of matrix metalloproteinases (MMPs) and very late antigens (VLAs). Furthermore, DMF treatment decreased the expression of Survivin and Bcl-extra large (Bcl-XL) proteins. CONCLUSION: Our results suggest that DMF as a novel inhibitor of NF-κB may be a potential therapeutic agent for metastatic melanoma.

High-Flow Nasal Cannula Therapy With Early Extubation for Subjects Undergoing Off-Pump Coronary Artery Bypass Graft Surgery.

BACKGROUND: The effects of high-flow nasal cannula (HFNC) therapy on postoperative atelectasis and duration of oxygen therapy after off-pump coronary artery bypass graft are unknown. The purpose of this study was to compare the effects of HFNC therapy for subjects who underwent off-pump coronary artery bypass graft with the effects of standard oxygen therapy in terms of oxygen requirement and atelectasis. METHODS: This prospective single-blinded randomized, controlled trial included 148 subjects who underwent off-pump coronary artery bypass graft between 2010 and 2015 with HFNC (n = 72) or without HFNC (standard O2, n = 76). The primary end point was the percentage difference in loss of lung volume between subjects with or without HFNC therapy. Secondary end points included the total amount of oxygen administered and duration of oxygen therapy with and without HFNC therapy. RESULTS: There were significant between-group differences in the percentage loss of lung volume (P < .001), total amount of oxygen administered (P < .001), duration of oxygen therapy (P < .001), and the need for postoperative diuretic therapy (P = .037). The amount (ρ = 0.569, P < .001) and duration (ρ = 0.678, P < .001) of oxygen administered were correlated with atelectasis volume. CONCLUSIONS: Using HFNC therapy after off-pump coronary artery bypass graft shortened the duration of oxygen therapy and reduced the percentage loss of lung volume and total amount of oxygen administered when compared with standard oxygen therapy.

RANKL-induced c-Src activation contributes to conventional anti-cancer drug resistance and dasatinib overcomes this resistance in RANK-expressing multiple myeloma cells.

The survival and growth of multiple myeloma (MM) cells are facilitated by cell-cell interactions with bone marrow stromal cells and the bone marrow microenvironment. These interactions induce de novo drug resistance known as cell adhesion-mediated drug resistance. Our previous results recently revealed that the receptor activator of NF-κB (RANK) ligand (RANKL), which is expressed by bone marrow stromal cells, contributes to anti-cancer drug resistance through the activation of various signaling molecules and suppression of Bim expression in RANK-expressing MM cells. However, the detailed mechanisms underlying RANKL-induced drug resistance remain uncharacterized. In the present study, we investigated the mechanism of RANKL-induced drug resistance in RANK-expressing MM cell lines. We found treatment of MM cells with RANKL-induced c-Src phosphorylation and activation of the downstream signaling molecules Akt, mTOR, STAT3, JNK, and NF-κB. In addition, treatment with dasatinib, a c-Src inhibitor, overcame RANKL- and bone marrow stromal cell-induced drug resistance to adriamycin, vincristine, dexamethasone, and melphalan by suppressing c-Src, Akt, mTOR, STAT3, JNK, and NF-κB activation and enhancing expression of Bim. Overall, RANKL- and bone marrow stromal cell-induced drug resistance correlated with the activation of c-Src signaling pathways, which caused a decrease in Bim expression. Dasatinib treatment of RANK-expressing MM cells re-sensitized them to anti-cancer drugs. Therefore, inhibition of c-Src may be a new therapeutic approach for overcoming RANKL-induced drug resistance in patients with MM.

Trametinib suppresses chemotherapy-induced cold and mechanical allodynia via inhibition of extracellular-regulated protein kinase 1/2 activation.

Chemotherapy-induced neuropathy is a common, dose-dependent adverse effect of some anti-cancer drugs and leads to discontinuation of chemotherapy and detrimental dose reductions, thereby affecting the quality of life of cancer patients. Currently, no treatment can effectively prevent or treat chemotherapy-induced neuropathy. Therefore, understanding its underlying molecular mechanisms may help to identify novel therapies for treating it. Some disease-induced neuropathy involve the activation of mitogen-activated protein kinases (MAPKs), such as extracellular-regulated protein kinase 1/2 (ERK1/2). In the present study, we investigated whether ERK1/2 inhibition can prevent chemotherapy-induced neuropathy. We found that trametinib, an MEK inhibitor, suppressed oxaliplatin-, paclitaxel-, vincristine-, and bortezomib-induced cold and mechanical allodynia in mice. In addition, treatment with oxaliplatin, paclitaxel, vincristine, or bortezomib enhanced ERK1/2 and c-Jun N-terminal kinase (JNK) phosphorylation in the spinal cord lumbar segments 4-6, and when combined with trametinib, can prevent chemotherapy-induced neuropathy via the suppression of ERK1/2 activation, but does not affect JNK activation. In conclusion, we demonstrated that the disruption of this pathway by MEK inhibitors suppresses oxaliplatin-, paclitaxel-, vincristine-, and bortezomib-induced neuropathy. This suggests that inhibition of the MEK/ERK pathway could prevent chemotherapy-induced neuropathy and MEK inhibitors could be used in combination with anti-tumor drugs during pharmacotherapy.

Rebamipide suppresses 5-fluorouracil-induced cell death via the activation of Akt/mTOR pathway and regulates the expression of Bcl-2 family proteins.

Oral mucositis is a common adverse effect of chemotherapy that limits the required dose of chemotherapeutic agents. Numerous attempts to mitigate chemotherapy-induced oral mucositis have failed to identify an appropriate treatment. Recently, it has been indicated that rebamipide prevents chemoradiotherapy-induced oral mucositis in patients. However, the details of the underlying mechanism involved in the cytoprotective effect of rebamipide remain obscure. In the present study, we investigated the mechanism behind rebamipide cytoprotective effect in the oral mucosa using primary normal human oral keratinocytes (NHOK cells). We found that rebamipide prevented 5-fluorouracil (5-FU)-induced cell death in NHOK cells. In addition, rebamipide increased the levels of phosphorylated Akt and mTOR, enhanced the Bcl-2 and Bcl-xL expressions, and suppressed the expression of Bax and Bim. This is in contrast to 5-FU-induced suppression of Akt and mTOR activation, Bcl-2 and Bcl-xL expressions, and the enhanced expression of Bax and Bim. These findings suggest that rebamipide can potentially be used for the protection of oral mucosa from chemotherapy-induced mucositis. This is the first study that elucidates the specific molecular pathway for the cytoprotective effect of rebamipide.

Long-term outcome in a case of translocated mitral valve replacement for massive mitral annular calcification.

Few reports have described long-term outcomes after translocated mitral valve replacement. We describe tips, potential pitfalls, and long-term outcome associated with the construction of a new mitral annulus and reinforcement of prosthesis attachment using a mitral prosthetic valve with an equine pericardial collar in a woman with extensive mitral valve calcification.

Outcomes of prosthetic valve replacement in women of child-bearing age.

PURPOSE: The outcomes of pregnancy are more favorable for women with bioprostheses than for those with mechanical prostheses. However, bioprostheses are associated with a high reoperation rate in young women and it remains unclear whether these young women can give birth without any complications. We analyzed the outcomes of prosthetic valve replacement and investigated the effectiveness and problems associated with bioprostheses in women of child-bearing age in Japan. METHODS: The subjects of this study were six consecutive young adult women aged under 40 years, who underwent prosthetic valve replacement between January 2007 and April 2016. RESULTS: Bioprostheses were selected for four of these six women in consideration of their child-bearing age. Mechanical valves were selected for the other two women who underwent the Konno procedure and double valve replacement (AVR, MVR) in view of their high risk for reoperation. The cardiac operations, although without mortality or morbidity, were complex and some involved multi-time procedures. Three of the women with bioprostheses had uneventful term pregnancies. CONCLUSIONS: These young women with bioprostheses were able to give birth safely; however, as multiple operations are often required, and bioprostheses may not be ideal for young women. Prosthetic valve selection for young women of child-bearing age requires adequate pregnancy counseling and long-term planning.

Aortic valve replacement in a patient with MPO-ANCA-positive Goodpasture disease.

Goodpasture disease (GD) is a rare autoimmune disorder characterized by the development of pathologic autoantibodies against both glomerular and alveolar basal membranes. Approximately one third of the patients with GD are also positive for anti-neutrophil cytoplasmic antibody (ANCA). In this case report, a 74-year-old woman was diagnosed as having myeloperoxidase (MPO)-ANCA-positive GD with severe aortic valve stenosis (AS). She underwent immunosuppressive therapy and plasmapheresis that led to GD remission. Whether a cardiac surgery affects a MPO-ANCA-positive GD in remission is unknown. We reported the outcomes after aortic valve replacement for severe AS in a patient with MPO-ANCA-positive GD.

Use of a Stent Graft for Patent Ductus Arteriosus in an Octogenarian Eliminates Ductus Flow.

Closure of a patent ductus arteriosus (PDA) in the elderly is a high-risk procedure because of tissue fragility and many possible complications. The patient in our case was an 81-year-old woman with a window-type PDA caused by cardiac failure. Based on the anatomy of the PDA and aorta and to minimize invasion, we used a stent graft to close the PDA. This approach was successful; hemodynamics improved and ductus flow was eliminated during the follow-up period without intervention from the pulmonary artery side.

[Ascending-descending Aortic Bypass and Aortic Valve Replacement for Aortic Coarctation with Bicuspid Aortic Valve and an Aberrant Right Subclavian Artery;Report of a Case].

A 53-year-old woman was developed congestive heart failure. She was diagnosed as having aortic coarctation, incompetent bicuspid aortic valve and an aberrant right subclavian artery by using echocardiography and enhanced computed tomography. Ankle brachial pressure index(ABI)in the right was 0.71 and 0.69 in the left. Blood pressure of the right arm was 60 mmHg lower than that of the left arm. To avoid perioperative adverse cardiac events due to a 2-staged operation, we performed ascending-descending aortic bypass and aortic valve replacement simultaneously through a median sternotomy. The heart was retracted cranially, and a vascular prosthesis was anastomosed to the descending aorta just above the diaphragm in an end-to-side manner. Then the graft was placed curvilinearly around the right atrium and was anastomosed to the ascending aorta. After the operation, the right and left ABI increased to 0.90 and 0.98 respectively. There was no pressure difference between the arms. The postoperative course was uneventful.

Identification of Coronary Artery Orifice to Prevent Coronary Complications in Bioprosthetic and Transcatheter Aortic Valve Replacement.

BACKGROUND: The aim of this study was to identify anatomical variations in coronary artery orifices among high-risk patients with a small aortic root undergoing bioprosthetic aortic valve replacement (BAVR) and transcatheter aortic valve replacement (TAVR) in order to prevent coronary orifice obstruction perioperatively. METHODS AND RESULTS: Coronary orifice and root structure were identified in 400 patients using aortic multidetector-row computed tomography (MDCT). We measured the aortic root diameter; intercommissural distances; and distance from coronary orifice to valve annulus, commissure, and sinotubular junction. We examined positional relationships between the coronary orifice and stent post, or sewing cuff of the bioprosthetic valve and leaflet of the transcatheter aortic valve. Most left coronary artery orifices were distributed near the center of the non-left and left-right commissures; right ones were relatively distributed on the non-right commissural side. Thirty-four patients (8.5%) with BAVR (coronary orifice near the commissure: 31, 7.8%; low takeoff: 5, 1.3%; and both: 2) and 39 (9.8%) with TAVR were at risk for coronary orifice obstruction. During BAVR, one-stitch rotation of the stent and one-stitch rotation with intra-annular implantation were used in near-commissure and low takeoff cases, respectively. During TAVR, percutaneous coronary intervention may be required in the height of the coronary orifice was ≤10 mm from the base of the ventricle aortic junction. CONCLUSIONS: Potential coronary complications during BAVR and TAVR in high-risk patients for coronary obstruction were identified using preoperative aortic MDCT. Choice of appropriate surgical technique or valve is essential.

Purulent pericardial effusion and mycotic pseudoaneurysm following insertion of a bare metal stent.

A 65-year-old male was diagnosed with purulent pericarditis, caused by Staphylococcus aureus five weeks after bare metal stenting for a 90% stenosis of the right coronary artery ostium. Subsequently, he developed a pseudoaneurysm in the right coronary sinus of Valsalva (CSV) requiring surgical intervention during the treatment of the pericarditis. Bacteremia after percutaneous coronary intervention (PCI) occurs in < 1% of patients and usually has insignificant clinical sequelae. We present an infected coronary bare metal stent of the proximal right coronary artery after PCI that resulted in a purulent pericardial effusion and mycotic pseudoaneurysm of the right coronary sinus of Valsalva (CSV). The patient successfully underwent surgical treatment.

Midterm results of left coronary artery reimplantation through the transverse sinus of the pericardium in adult Bland-White-Garland syndrome.

The anomalous origin of the left coronary artery from the pulmonary artery - known as Bland-White-Garland syndrome - is a rare congenital malformation that affects 1 in 300,000 live births. Most patients die in infancy without any surgical treatment. Some patients who survive past childhood often have varying symptoms such as myocardial ischemia, impaired left ventricular function, mitral regurgitation, and progressive heart failure, depending on the development collateral circulation. In the present report, we describe a procedure wherein the left coronary artery ostium was translocated through the transverse sinus of the pericardium in a 43-year-old mother with Bland-White-Garland syndrome and concomitant mitral regurgitation and report on the associated midterm results.

Mitral valve plasty in an adult patient without a right superior vena cava.

Persistent left superior vena cava without a right superior vena cava is an extremely rare condition. We report the case of a 65-year-old woman with this condition who underwent mitral valve plasty. During cardiac catheterization, the asymptomatic patient with mitral valve prolapse syndrome was found to have a persistent left superior vena cava without a right superior vena cava. During mitral valve plasty, cardiopulmonary bypass was established using bicaval drainage through the persistent left superior vena cava and the right atrium. A cannula was inserted into the persistent left superior vena cava to provide a large surgical field in the left atrium. We selected a technique that involved direct insertion of an L-shaped cannula into the persistent left superior vena cava and obtained a clear view of the surgical field. Proper assessment of the right superior vena cava is necessary when a persistent left superior vena cava is suspected.

Usefulness of an enhanced recovery after surgery protocol for perioperative management following open repair of an abdominal aortic aneurysm.

PURPOSE: To achieve early recovery and early discharge from the hospital by applying an enhanced recovery after surgery (ERAS) protocol, which is mainly used with colonic surgery, for the perioperative management of open AAA surgery. METHOD: One hundred twenty-seven open AAA surgery cases successfully carried out between 2003 and 2011 were included in this study. The ERAS protocol was used for the cases from April 2008 onward, and we performed a comparison of the conventionally treated cases with ERAS cases regarding the start of postoperative oral consumption, the postoperative hospital stay, and hospitalization medical costs. RESULTS: The time to restarting oral consumption and the postoperative hospital stay were significantly shorter for the ERAS group (n = 52) compared to the conventionally managed group (n = 75); with values of 59 ± 15 and 93 ± 25 h (p = 0.021), 9 ± 3 and 16 ± 5 days (p = 0.001), respectively. The medical costs for the ERAS group were 92 % of the costs of the conventionally managed group. CONCLUSION: Use of the ERAS protocol for the perioperative management of open AAA surgery shortened the time before recommencing oral consumption, the postoperative hospital stay, and reduced the medical costs compared to the conventional approach.

Histopathology of the longest-lived saphenous vein graft in a patient with Kawasaki disease.

The patency rate of saphenous vein grafts (SVGs) for children with Kawasaki disease (KD) tends to decline during the early years after coronary artery bypass grafting (CABG). Although degenerative changes have been considered the main cause of SVG occlusion, there have been no reports on the histopathologic features of the SVG in patients with KD. We herein describe a redo off-pump total arterial revascularization in a 43-year-old man with KD, 34 years after the first CABG using SVG. The histopathologic examination of the longest-lived SVG demonstrated that graft occlusion was mainly caused by the diffuse intimal hyperplasia.