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.

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.

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.

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.

[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.

Simple and efficient method for generation of induced pluripotent stem cells using piggyBac transposition of doxycycline-inducible factors and an EOS reporter system.

PiggyBac (PB) transposition of reprogramming factors (Oct3/4 (O), Sox2 (S), Klf4 (K) and c-Myc) is a safe, nonviral method for generating induced pluripotent stem cells (iPSCs). However, compared with retroviral methods, the reprogramming efficiency of the PB-mediated methods is relatively low. In this study, we describe a simple and efficient system for generating high-quality iPSCs by a single transfection of multiple plasmids that does not require the use of a virus, special instruments or skilled techniques. To improve reprogramming efficiency, we modified the components of the polycistronic 2A vectors used in this study and also investigated the combination of another reprogramming-related factor (L-Myc). By simultaneous transposition of multiple PB vectors containing an EOS (early transposon promoter and Oct3/4 and Sox2 enhancers) reporter and modified polycistronic doxycycline (Dox)-inducible factors, we reprogrammed mouse somatic cells with an efficiency higher than is usually obtained with retroviral methods and we established some iPSC lines that contributed highly to chimeras. By using the Dox-inducible system, we also showed that the appropriate elimination of exogenous-factor expression at appropriate time accelerated the induction of Oct3/4 when a combination of OKS and c-Myc vectors were used.

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.

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.

Cardiac lipoma originating from the left ventricular apex diagnosed using the magnetic resonance imaging fat suppression technique: report of a case.

A 70-year-old male patient had a tumor in the left ventricular apex that was detected by transthoracic echocardiography. He had no clinical manifestations. A diagnosis of benign lipoma was made using the noninvasive fat suppression technique of cardiac magnetic resonance imaging (MRI). Video-assisted surgery was performed to resect the tumor, and the histopathological examination confirmed the diagnosis of lipoma. A small part of the tumor was not resected. The postoperative course was uneventful. No signs of recurrence were detected on transthoracic echocardiography or MRI during a 22-month post surgical follow-up period.

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.

Premeditated reoperation after mitral valve replacement with a Starr-Edwards ball valve for young women who desire to bear a child: report of two cases.

There are many difficulties for young women with a Starr-Edwards ball valve who want to attempt pregnancy. There is no consensus regarding whether they should maintain anticoagulation therapy throughout pregnancy with the risk of a thromboembolism or to undergo a reoperation with bioprosthetic heart valves, followed by a third operation when the valve deteriorates. This report presents two cases of young women who underwent mitral valve replacement (MVR) with Starr-Edwards ball valves (model 6120: 1M) during their childhood. Although they did not have any cardiac symptoms, transthoracic echocardiography and cardiac catheterization data demonstrated that both the patients had asymptomatic mild relative mitral stenosis. They both wished to bear a child. After the patients and their family provided thorough informed consent, redo MVRs were preformed safely with biological prostheses. The presence of significant pannus formation along the strut and sewing ring of the excised valves could also have a positive impact on the decision to undergo reoperation.

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.

Early angiographic results of multivessel off-pump coronary artery bypass grafting.

OBJECTIVES: Recently off-pump coronary artery bypass grafting (CABG) is being widely used for coronary revascularization. However, there is some evidence that off-pump surgery increases the risk of recurrent angina and the need for reintervention, suggesting poor graft quality or incomplete revascularization. We describe our experience to demonstrate the feasibility of multiple coronary revascularization in off-pump CABG (OPCAB). PATIENTS AND METHODS: From January 2002 to March 2003, 168 patients underwent OPCAB at our institute. In 16 of them, 6 to 9 vessels were revascularized in each patient. There were 14 males and 2 females with a mean age of 66 years (47 to 74 years). All patients had triple-vessel disease. Ten patients received in situ arterial grafts only which were harvested with the skeletonization technique using an ultrasonic scalpel. We used the Starfish heart positioner to expose lateral, posterior, and inferior walls of the heart with minimal hemodynamic compromise. RESULTS: All patients were discharged from the hospital without any serious complications. Postoperative angiography was performed in 87.5% within 1 month after operation. The patency rate was 96.6%. CONCLUSION: These results indicate that complete revascularization can be achieved in OPCAB in patients with diffuse coronary arterial disease. Complete revascularization with in situ arterial conduits only is technically feasible and yields a high early graft patency, even in the off-pump situation.

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.