Impact of sarcopenia on long-term survival after cardiac surgery for end-stage renal disease patients.

BACKGROUND: The long-term mortality of end-stage renal disease (ESRD) patients is still unsatisfactory. Therefore, long-term risk assessments in ESRD patients undergoing cardiac surgery are needed. Recently, sarcopenia is major concern in cardiac surgery because of its association with poor long-term survival. However, the impact of sarcopenia on the long-term survival of ESRD patients undergoing cardiac surgery is not well understood. METHODS: Eighty-two ESRD patients who underwent elective cardiac surgery were enrolled. Sarcopenia was identified based on noncontrast abdominal computed tomography. The impact of preoperative and intraoperative factors on long-term survival was investigated. RESULTS: Forty-three patients (52%) were diagnosed with sarcopenia. The in-hospital mortality rate was 4.9%. The 5-year overall survival rate was 48%. The multivariate analyses revealed that STS score ≥ 4 (odds ratio, 6.0; confidence interval, 2.5-14.7; p < 0.01) and presence of sarcopenia (odds ratio, 2.4; confidence interval, 1.3-4.5; p = 0.03) were independent risk factors for overall survival. The 5-year survival rates of low-risk (Society of Thoracic Surgeons score of < 4) patients without sarcopenia, low-risk with sarcopenia, more than intermediate-risk (Society of Thoracic Surgeons score of ≥ 4) without sarcopenia, and more than intermediate-risk with sarcopenia groups were 80%, 51%, 50%, and 26%, respectively. CONCLUSIONS: Among the ESRD patients, the low risk without sarcopenia group showed an excellent long-term survival, in contrast to more than intermediate-risk patients with sarcopenia, who can expect poor long-term survival. Preoperative assessment of sarcopenia in addition to the surgical risk score can be useful in developing a therapeutic strategy.

2,5-Dimethylcelecoxib attenuates cardiac fibrosis caused by cryoinjury-induced myocardial infarction by suppressing the fibroblast-to-myofibroblast transformation via inhibition of the TGF-ß signaling pathway.

We previously reported that 2,5-dimethylcelecoxib (DM-C), a derivative of celecoxib, lacks cyclooxygenase-2 inhibitory effects and suppresses cardiac remodeling by activating glycogen synthase kinase-3 (GSK-3). However, it remains unclear whether DM-C attenuates fibroblast-to-myofibroblast transformation (FMT), which plays a key role in cardiac fibrosis. Therefore, we evaluated the effect of DM-C on FMT using a cryoinjury-induced myocardial infarction (CMI) mouse model. We found that DM-C attenuated the deterioration of left ventricular ejection fraction after CMI by decreasing cardiac fibrosis. Analysis of the expression level of α-smooth muscle actin (α-SMA), a marker for myofibroblasts, indicated that DM-C decreased FMT at the cardiac injury site. To investigate the mechanism by which DM-C attenuated FMT, fibroblasts obtained from the heart were stimulated with TGF-ß to induce FMT, and the effect of DM-C was analyzed. DM-C suppressed the expression of α-SMA and the phosphorylation levels of Smad 2/3 and GSK-3, indicating that DM-C suppressed α-SMA expression by inhibiting the transforming growth factor (TGF)-ß signaling pathway via activation of GSK-3. DM-C decreased the expression of collagen, connective tissue growth factor (CTGF) and Snail, which are also known to accelerate cardiac fibrosis. These results suggested that DM-C attenuated cardiac fibrosis by suppressing FMT at the injured site after CMI by inhibiting the TGF-ß signaling pathway via activation of GSK-3. Thus, DM-C has potential against cardiac disease as a novel anti-fibrotic agent.

Differentiation-inducing factor-1 potentiates adipogenic differentiation and attenuates the osteogenic differentiation of bone marrow-derived mesenchymal stem cells.

Mesenchymal stem cells (MSCs) are an attractive cell source for tissue regeneration and repair. However, their low differentiation efficacy currently impedes the development of MSC therapy. Therefore, in this study, we investigated the effects of differentiation-inducing factor-1 (DIF-1) on the differentiation efficacy of bone marrow-derived MSCs (BM-MSCs) into adipogenic or osteogenic lineages. BM-MSCs, which were obtained from Sprague-Dawley rats, were positive for the MSC markers (CD29, CD73, and CD90). DIF-1 alone neither affected cell surface antigen expression nor induced adipogenic or osteogenic differentiation. However, DIF-1 significantly enhanced the effects of adipogenic differentiation stimuli, which were evaluated as the number of oil red-O positive cells and the expression of adipocyte differentiation markers (peroxisome proliferator-activated receptor gamma, adipocyte fatty acid-binding protein, and adiponectin). In contrast, DIF-1 significantly attenuated the effects of osteogenic differentiation stimuli, which were evaluated as alizarin red-S positive calcium deposition, and the expression of osteoblast differentiation markers alkaline phosphatase, runt-related transcription factor 2, and osteopontin. We further investigated the mechanism by which DIF-1 affects MSC differentiation efficacy and found that glycogen synthase kinase-3 was the main factor mediating the action of DIF-1 on the adipogenic differentiation of BM-MSCs, whereas it was only partially involved in osteogenic differentiation. These results suggest that DIF-1 supports MSC differentiation toward the desired cell fate by enhancing the differentiation efficacy.

Significant delayed aortic dilatation after tetralogy of Fallot repair: a case report.

BACKGROUND: Aortic dilatation may occur in some patients even after complete repair of tetralogy of Fallot (TOF). The progression rate of the aortic diameter is so slow, and the incidence of aortic dissection is so low that it is suspected that frequent imaging of the aorta may not be necessary. CASE PRESENTATION: We describe an asymptomatic 41-year-old man with hypertension in whom aortic dilatation was accidentally discovered 39 years after TOF repair. He underwent ambulatory follow-up without any difficulty for 21 years after the repair. Contrast-enhanced computed tomography revealed significant aortic dilatation (maximum diameter of 88 mm at the sinus of Valsalva), and echocardiography revealed severe aortic regurgitation, which seemed to progress during the last 18 years without any evaluation or follow-up. The Bentall procedure was successfully performed using a valved graft, under deep hypothermic circulatory arrest with antegrade cerebral perfusion, and his postoperative course was uneventful. Histopathological examination of ascending aorta specimens revealed severe cystic medial degeneration. CONCLUSIONS: Keeping in mind that a patient with rapid progression of the aortic dilatation after TOF repair exist, periodic follow-up for evaluation of the aorta is essential in patients with TOF.

Atypical Hemolytic Uremic Syndrome following Acute Type A Aortic Dissection.

Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy (TMA)-related disease that manifests as a triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury (AKI) and is caused by uncontrolled activation of the complement system. We report the case of a 61-year-old woman with acute type A aortic dissection that subsequently developed into aHUS. The hematologic disorders underlying aHUS improved after treatment with the complement inhibitor eculizumab. It is important to consider aHUS when a patient clinically develops a triad of microangiopathic hemolytic anemia, thrombocytopenia, and an increasing creatinine level following cardiovascular surgery.

Surgical Therapy for Patients with Severe Aortic Stenosis in the Era of Transcatheter Aortic Valve Replacement.

Aortic stenosis (AS) is the most common valvular heart disease and is most frequently recognized among elderly people. Surgical aortic valve replacement (SAVR) is the most effective therapy, but its indication is sometimes difficult, and is impossible for high operative risk patients. Transcatheter aortic valve replacement (TAVR) was recently approved in Japan for high risk and inoperable patients with severe AS. TAVR is a less invasive method because it does not require a cardiopulmonary bypass and is associated with excellent surgical outcomes. In Western countries, the indication of TAVR has already been extended to moderate operative risk patients with severe AS, and is going to be further extended to low risk patients. The number of patients undergoing TAVR is increasing progressively, and there are effective alternative therapies for patients with severe AS. Selection of these surgical methods will be important in the near future. In regard to low operative risk patients especially, not only operative mortality, but also long-tern mortality and morbidity and quality of life should be taken into consideration. It is considered that some comorbidities in AS patients will be revealed to have an impact on surgical outcomes at the time when these surgical methods are selected. In this review, we examine end-stage renal disease on hemodialysis, functional tricuspid regurgitation, and sigmoid septum, and give an outline of what influence SAVR and TAVR have on the surgical outcomes of severe AS patients.

[A Case of Successful Surgery for Adult Partial Atrioventricular Septal Defect].

We report a case of a 55-year-old male who had been diagnosed with mitral regurgitation and atrial septal defect 5 years earlier. He was referred to our institution because of worsening of mitral regurgitation accompanied by exertional dyspnea. As an echocardiography showed atrioventricular valve regurgitation and ostium primum atrial septal defect, but without ventricular septal defect, he was diagnosed as having partial atrioventricular septal defect (pAVSD). An operation was performed through median sternotomy. The anterior atrioventricular leaflet had a cleft and thickening with calcification. Suturing the cleft could not control the regurgitation. Incomplete coaptation was seen at the edge of the anastomosis site of the cleft, where the severe calcification had been identified. A rough zone including a part of the chordae tendineae was sutured in order to compensate for the gap. The atrioventricular septal defect was closed with an autologous pericardial patch. He was discharged uneventfully on the 24th postoperative day and has been followed up without complications for 1.5 years.

Salvage surgery combined with descending aorta resection for lung cancer.

BACKGROUND: Recent retrospective studies have shown that salvage surgery can improve survival with acceptable adverse events, and this procedure has been adapted for lung cancer. However, there are no reports demonstrating the efficacy of salvage surgery combined with aortic resection. CASE PRESENTATION: A 73-year-old man had received definitive concurrent chemoradiotherapy (carboplatin/paclitaxel, 70 Gy) for lung cancer originated from the left upper lobe and infiltrating the thoracic aorta (cT4N1M0 stage IIIA). Although the tumor has shrunk significantly (ycT4N0M0 stage IIIA), radiation pneumonitis occurred. Due to the steroid therapy, radiation pneumonitis was relieved; however, re-enlargement of the primary tumor was observed during steroid tapering. Nonetheless, the lymphatic and distant metastases were controlled. Moreover, aortic invasion was localized to the periphery of the third branch, and the tumor was considered to be resectable. Intraoperatively, we observed macroscopic evidence of aortic invasion in the periphery of the third branch; thus, left upper lobectomy combined with descending aorta resection was performed under partial extracorporeal circulation. The patient is currently active without any recurrence 21 months post-surgery. CONCLUSIONS: No clear consensus exists regarding salvage surgery combined with aortic resection for primary lung cancer. However, we believe that this surgery may improve the survival of carefully selected patients.