Cor Triatriatum in the Adult with Aortic Stenosis and Mitral Stenosis

Background：Cor triatriatum is a rare congenital cardiac anomaly, in which the left atrium or right atrium is separated by an abnormal fibromuscular membrane with one or more restrictive orifices. This condition typically presents in infancy or early childhood and can be associated with other cardiac anomalies.Case presentation：A 75-year-old woman was admitted for exertional dyspnea with moderate aortic and mitral stenosis. As cor triatriatum was revealed by a computed tomography and echocardiography, she was referred to our department for surgery. Aortic valve replacement, mitral valve replacement and excision of the membranous septum in the left atrium was performed. This report presents an incidental findings of cor triatriatum with aortic stenosis, moderate mitral stenosis in septuagenarian.Conclusion：We encountered a rare case of cor triatriatum with aortic stenosis and mitral stenosis in septuagenarian. She was incidentally diagnosed by rheumatic aortic and mitral stenosis which had advanced to moderate level

CCL2 as a potential therapeutic target for clear cell renal cell carcinoma

We previously reported that the pVHL-atypical PKC-JunB pathway contributed to promotion of cell invasiveness and angiogenesis in clear cell renal cell carcinoma (ccRCC), and we detected chemokine (C-C motif) ligand-2 (CCL2) as one of downstream effectors of JunB. CCL2 plays a critical role in tumorigenesis in other types of cancer, but its role in ccRCC remains unclear. In this study, we investigated the roles and therapeutic potential of CCL2 in ccRCC. Immunohistochemical analysis of CCL2 expression for ccRCC specimens showed that upregulation of CCL2 expression correlated with clinical stage, overall survival, and macrophage infiltration. For functional analysis of CCL2 in ccRCC cells, we generated subclones of WT8 cells that overexpressed CCL2 and subclones 786-O cells in which CCL2 expression was knocked down. Although CCL2 expression did not affect cell proliferation in vitro, CCL2 overexpression enhanced and CCL2 knockdown suppressed tumor growth, angiogenesis, and macrophage infiltration in vivo. We then depleted macrophages from tumor xenografts by administration of clodronate liposomes to confirm the role of macrophages in ccRCC. Depletion of macrophages suppressed tumor growth and angiogenesis. To examine the effect of inhibiting CCL2 activity in ccRCC, we administered CCL2 neutralizing antibody to primary RCC xenografts established from patient surgical specimens. Inhibition of CCL2 activity resulted in significant suppression of tumor growth, angiogenesis, and macrophage infiltration. These results suggest that CCL2 is involved in angiogenesis and macrophage infiltration in ccRCC, and that CCL2 could be a potential therapeutic target for ccRCC

Functional and genomic characterization of patient‐derived xenograft model to study the adaptation to mTORC1 inhibitor in clear cell renal cell carcinoma

Resistance to the mechanistic target of rapamycin (mTOR) inhibitors, which are a standard treatment for advanced clear cell renal cell carcinoma (ccRCC), eventually develops in most cases. In this study, we established a patient-derived xenograft (PDX) model which acquired resistance to the mTOR inhibitor temsirolimus, and explored the underlying mechanisms of resistance acquisition. Temsirolimus was administered to PDX model mice, and one cohort of PDX models acquired resistance after repeated passages. PDX tumors were genetically analyzed by whole-exome sequencing and detected several genetic alterations specific to resistant tumors. Among them, mutations in ANKRD12 and DNMT1 were already identified in the early passage of a resistant PDX model, and we focused on a DNMT1 mutation as a potential candidate for developing the resistant phenotype. While DNMT1 expression in temsirolimus-resistant tumors was comparable with the control tumors, DNMT enzyme activity was decreased in resistant tumors compared with controls. Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9-mediated heterozygous knockdown of DNMT1 in the temsirolimus-sensitive ccRCC (786-O) cell line was shown to result in a temsirolimus-resistant phenotype in vitro and in vivo. Integrated gene profiles using methylation and microarray analyses of PDX tumors suggested a global shift for the hypomethylation status including promotor regions, and showed the upregulation of several molecules that regulate the mTOR pathway in temsirolimus-resistant tumors. Present study showed the feasibility of PDX model to explore the mechanisms of mTOR resistance acquisition and suggested that genetic alterations, including that of DNMT1, which alter the methylation status in cancer cells, are one of the potential mechanisms of developing resistance to temsirolimus

Aortic Valve Replacement in Anomalous Aortic Origin of Right Coronary Artery

A 75-year-old man with severe aortic regurgitation was referred to our department for surgery. Coronary angiography revealed 75% stenosis at left coronary artery( LAD) and a normally positioned left coronary artery. However, the location of the right coronary artery was anomalous. The right coronary artery ostium originated from the ascending aorta above the left coronary cusp. Emergency surgery proceeded to address severe dyspnea due to congestive heart failure. The higher portion of the right coronary artery was incised in sigmoid fashion, the aortic valve was replaced with a 23-mm stented bioprosthesis and coronary bypass grafting proceeded. The postoperative course was uneventful

Hemolytic Anemia soon after Replacement of Ascending Aorta for acute Aortic Dissection

A 61-year-old female underwent replacement of the ascending aorta for Type A aortic dissection, then gradually developed severe hemolytic anemia over 1 month. The cause of hemolysis was found to be mechanical damage of red blood cells caused by an inverted felt strip at the proximal anastomosis. A reoperation for resection of the felt and repair of the proximal anastomosis successfully resolved the problem. Here, we report a rare case of hemolytic anemia at the site of an inverted felt strip that occurred after replacement of the ascending aorta

Modified Bentall operation with bioprosthetic valve and Valsalva graft conduit:the "slit skirt" technique

We elucidated the efficacy of the slit skirt technique to prevent bleeding from the proximal anastomosis between the graft and aortic annulus. Between September 2008 and September 2014, 15 patients underwent a modified Bentall operation with the slit skirt technique at our institution. No patients had bleeding from the proximal anastomosis. No re-thoracotomy for bleeding was required. During midterm follow-up (median period, 21 months), no patient had pseudoaneurysms at the proximal suture line. We conclude that the slit skirt technique is useful to prevent bleeding from the proximal anastomosis after the Bentall operation

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

A ROENTGENOCEPHALOMETRIC STUDY ON THE POSITION OF THE HYOID BONE

The position of the hyoid bone as related to the cranial base and to the mandible was investigated. The materials used in this study were twenty Japanese adults of both sexes with normal occlusion, and twenty orthodontic cases with upper protrusion (Angle Class II division 1), and twenty lower protrusion cases (Angle Class III). The Hellman’s dental age analysis of these clinical cases was between III-C and IV-A. The position of the body of the hyoid as related to the cranial base showed a significant difference among· these three groups. Compared with the normal occlusion group, the body of the hyoid was located slightly backward in the upper protrusion group and slightly forward in the lower protrusion. However, in relation to the mandible, position of the body of the hyoid was constant in these three groups. In order to confirm the stability of the relative position of the hyoid to the mandible, following two cases were investigated; an ankylosis of the temporomandibular joint and a case of lower protrusion with severe distortion of the cervical vertebra caused by tuberculosis of spines. In the former case, the mandible was located far backward in relation to the cranium, while that of the latter was located far forward. However, the relative position of the hyoid to the mandible seemed to be stable in these two cases. The hyoid as related to the cranial base varied when the mandible took anteroposterior malpositions to the cranium. Considering the fact that the hyoid position as related to the mandible was stable, the muscles which connect them seemed to play an important role in the displacement of the mandible