Characteristics of Inoperable Patients with Severe Aortic Valve Stenosis —In the Era of Transcatheter Aortic Valve Replacement

Purpose: Transcatheter aortic valve replacement (TAVR) has emerged as a therapeutic option for severe aortic valvular stenosis (AS). To determine the indication for TAVR, it is mandatory to clarify the characteristics of the patients who were judged as inoperable for conventional aortic valve replacement (cAVR).Methods: Of 185 patients newly diagnosed as severe AS from March 2010 to April 2011, we studied the characteristics of 61 (33%) patients (mean age, 86 ± 8 years) who were judged as inoperable.Results: Younger patients (<85 years old, n = 22) had more major comorbidities and lower left ventricular ejection fraction than older patients (≥85 years old, n = 39). Mean estimated mortality for cAVR by Japan score was 7.0% ± 7.4%. Japan score did not correlate to age and was calculated relatively low in the older age group (6.2% ± 7.0%) than the younger age group (8.3% ± 8.1%).Conclusion: One thirds of severe AS patients were judged as inoperable. In advanced age patients, age itself and other factors, which are not included in the conventional scoring systems, might have contributed to the decision making not to perform cAVR by cardiologists. Further study is necessary to define risk factors except for age.     

Selective expansion of donor‐derived regulatory T cells after allogeneic bone marrow transplantation in a patient with IPEX syndrome

IPEX syndrome is a rare and fatal disorder caused by absence of regulatory T cells (Tregs) due to congenital mutations in the Forkhead box protein 3 gene. Here, we report a patient with IPEX syndrome treated with RIC followed by allogeneic BMT from an HLA‐matched sibling donor. We could achieve engraftment and regimen‐related toxicity was well tolerated. Although the patient was in mixed chimera and the ratio of donor cells in whole peripheral blood remained relatively low, selective and sustained expansion of Tregs determined as CD4+CD25+Foxp3+ cells was observed. Improvement in clinical symptoms was correlated with expansion of donor‐derived Tregs and disappearance of anti‐villin autoantibody, which was involved in the pathogenesis of gastrointestinal symptoms in IPEX syndrome. This clinical observation suggests that donor‐derived Tregs have selective growth advantage in patients with IPEX syndrome even in mixed chimera after allogeneic BMT and contribute to the control of clinical symptoms caused by the defect of Tregs.     

Salivary duct carcinoma in the mandible: a case report

Salivary duct carcinoma (SDC) is a distinctive and aggressive neoplasm. The most frequent site of origin is the parotid gland, followed by the submandibular gland. SDC originating in the minor salivary glands, particularly in the ectopic glands within the mandible, is extremely rare. We describe a 62-year-old man with SDC in the mandible, who presented with a painless lump in the right submandibular region (later identified as lymph node metastasis) and ipsilateral mental nerve palsy. Histologic examination after ablative surgery revealed SDC originating in the mandible and cervical nodal metastases spreading to levels I-III. The patient remains alive 59 months after presentation as a result of postoperative full-dose irradiation and regular intensive chemotherapy using TXT, 5-FU, and CDDP. However, the patient has local recurrence and distant metastases to the lung and brain. In this report, we also discuss the specific diagnostic criteria and developmental theories of intraosseous salivary gland tumors.     

An immunohistochemical and ultrastructural study of the pericellular matrix of uneroded hypertrophic chondrocytes in the mandibular condyle of aged c-src-deficient mice

OBJECTIVE: Previous studies indicate that hypertrophic chondrocytes can transdifferentiate or dedifferentiate and redifferentiate into bone cells during the endochondral bone formation. Mandibular condyle in aged c-src-deficient mice has incremental line-like striations consisting of cartilaginous and non-cartilaginous layers, and the former contains intact hypertrophic chondrocytes in uneroded lacunae. The purpose of this study is to determine the phenotype changes of uneroded hypertrophic chondrocytes. DESIGN: Immunohistochemical and ultrastructural examinations of the pericellular matrix of hypertrophic chondrocytes in the upper, middle, and lower regions of the mandibular condyle were conducted in aged c-src-deficient mice, using several antibodies of cartilage/bone marker proteins. RESULTS: Co-localisation of aggrecan, type I collagen, and dentin matrix protein-1 (DMP-1) or matrix extracellular phosphoprotein (MEPE) was detected in the pericellular matrix of the middle region. Ultrastructurally, granular substances in the pericellular matrix of the middle region were the remains of upper region chondrocytes, which were mixed with thick collagen fibrils. In the lower region, the width of the pericellular matrix and the amount of collagen fibrils were increased. Versican, type I collagen, DMP-1, and MEPE were detected in the osteocyte lacunae. Additionally, DMP-1 and MEPE were detected in the pericellular matrix of uneroded hypertrophic chondrocytes located in the lower, peripheral region of the mandibular condyle in younger c-src-deficient mice, but not in the aged wild-type mice. CONCLUSIONS: These results indicate that long-term survived, uneroded hypertrophic chondrocytes, at least in a part, acquire osteocytic characteristics.     

Formation of acellular cementum-like layers, with and without extrinsic fiber insertion, along inert bone surfaces of aging c-Src gene knockout mice

To investigate the long-term effects of c-src deficiency on skeletal and dental tissues, we examined the lower jaws and long bones of c-src gene knockout (c-src KO) mice by histological and histochemical methods. Numerous multinucleated osteoclasts were distributed throughout the mandible in 5-wk-old c-src KO mice, but by 14 wk they had almost completely disappeared from the alveolar bone, leaving tartrate-resistant acid phosphatase (TRAP)-positive layers along the bone surface. Deposition of osteopontin-positive mineralized tissue, reminiscent of acellular afibrillar cementum (AAC), was confirmed along the TRAP-positive bone surface at 14 wk. The layer progressively thickened up to 21 months. A comparable mineralized layer was noted along the trabeculae of long bones as thickened cement lines. In the periostin-rich areas of jaw bones, but not in the long bones, portions of AAC-like mineralized layers were often replaced with and/or covered by acellular extrinsic fiber cementum (AEFC)-like tissue. These data suggest that the deposition of AAC-like mineralized tissue is a general phenomenon that may occur along inert or slowly remodeling bone surfaces under conditions characterized by reduced bone-resorbing activity, whereas the induction of AEFC-like tissue seems to be associated with the expression of certain molecules that are particularly abundant in the microenvironment of the periodontal ligament.