Efficacy of Computed Tomography-Based Evaluation of Myocardial Extracellular Volume Combined With Red Flags for Early Screening of Concealed Cardiac Amyloidosis in Patients With Atrial Fibrillation.

BACKGROUND: The prevalence of transthyretin amyloid cardiomyopathy (ATTR-CM) in atrial fibrillation (AF) patients remains unclear. We explored the efficacy of computed tomography-based myocardial extracellular volume (CT-ECV) combined with red flags for the early screening of concealed ATTR-CM in AF patients undergoing catheter ablation.Methods and Results: Patients referred for AF ablation at Oita University Hospital were prescreened using the red-flag signs defined by echocardiographic or electrocardiographic findings, medical history, symptoms, and blood biochemical findings. Myocardial CT-ECV was quantified in red flag-positive patients using routine pre-AF ablation planning cardiac CT with the addition of delayed-phase cardiac CT scans. Patients with high (>35%) ECV were evaluated using technetium pyrophosphate (99 mTc-PYP) scintigraphy. A cardiac biopsy was performed during the planned AF ablation procedure if 99 mTc-PYP scintigraphy was positive. Between June 2022 and June 2023, 342 patients were referred for AF ablation. Sixty-seven (19.6%) patients had at least one of the red-flag signs. Myocardial CT-ECV was evaluated in 57 patients because of contraindications to contrast media, revealing that 16 patients had high CT-ECV. Of these, 6 patients showed a positive 99 mTc-PYP study, and 6 patients were subsequently diagnosed with wild-type ATTR-CM via cardiac biopsy and genetic testing. CONCLUSIONS: CT-ECV combined with red flags could contribute to the systematic early screening of concealed ATTR-CM in AF patients undergoing catheter ablation.

Empagliflozin Suppresses the Differentiation/Maturation of Human Epicardial Preadipocytes and Improves Paracrine Secretome Profile.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce epicardial adipose tissue (EAT) in humans, enhancing cardioprotective effects on heart failure and atrial fibrillation. We investigated the direct effect of the SGLT2 inhibitor empagliflozin on human primary epicardial adipocytes and preadipocytes. SGLT2 is primarily expressed in human preadipocytes in the EAT. The expression levels of SGLT2 significantly diminished when the preadipocytes were terminally differentiated. Adipogenesis of preadipocytes was attenuated by empagliflozin treatment without affecting cell proliferation. The messenger RNA levels and secreted protein levels of interleukin 6 and monocyte chemoattractant protein 1 were significantly decreased in empagliflozin-treated adipocytes. Coculture of human induced pluripotent stem cell-derived atrial cardiomyocytes and adipocytes pretreated with or without empagliflozin revealed that empagliflozin significantly suppressed reactive oxygen species. IL6 messenger RNA expression in human EAT showed significant clinically relevant associations. Empagliflozin suppresses human epicardial preadipocyte differentiation/maturation, likely inhibiting epicardial adipogenesis and improving the paracrine secretome profile of EAT, particularly by regulating IL6 expression.

Association between interatrial septum adiposity and atrial fibrillation: transesophageal echocardiography imaging and autopsy study.

Recent clinical evidence has suggested that interatrial septal (IAS) adiposity contributes to atrial fibrillation (AF). The present study aimed to confirm the usefulness of transesophageal echocardiography (TEE) to estimate IAS adiposity in patients with AF. The histological IAS analysis based on autopsy samples sought to clarify characteristics that underlie the contribution of IAS adiposity to AF. The imaging study analyzed the TEE results in patients with AF (n = 184) in comparison with transthoracic echocardiography (TTE) and computed tomography (CT) results. The autopsy study histologically analyzed IAS in subjects with (n = 5) and without (n = 5) history of AF. In the imaging study, the ratio of interatrial septum adipose tissue (IAS-AT) volume per epicardial adipose tissue (EpAT) volume was greater in patients with persistent AF compared (PerAF) to those with paroxysmal AF (PAF). Multivariable analysis revealed that both TEE-assessed IAS thickness and TTE-assessed left atrial dimension were predicted by CT-assessed IAS-AT volume. In the autopsy study, the histologically-assessed IAS section thickness was greater in the AF group than that in the non-AF group and was positively correlated with the IAS-AT area percentage. In addition, the size of adipocytes in IAS-AT was smaller, compared to EpAT and subcutaneous adipose tissue (SAT). IAS-AT infiltrated into the IAS myocardium, as if adipose tissue split the myocardium (designated as myocardial splitting by IAS-AT). The number of island-like myocardium pieces as a result of myocardial splitting by IAS-AT was greater in the AF group than in the non-AF group and was positively correlated with the IAS-AT area percentage. The present imaging study confirmed the usefulness of TEE to estimate IAS adiposity in patients with AF without radiation exposure. The autopsy study suggested that the myocardial splitting by IAS-AT may contribute to atrial cardiomyopathy leading to AF.

A Case of Vascular Malformation in the Buccal Fat Pad.

Vascular anomalies are categorized as vascular tumors or vascular malformations (VMs) based on the system of classification (updated in 2018) established by the International Society for the Study of Vascular Anomalies. In the orofacial region, such anomalies are most likely to occur in the lips or tongue, and only rarely in the buccal fat pad. This report describes a case of a VM in the buccal fat pad. A 47-year-old woman was referred to our hospital with a mass lesion in her left cheek. On palpation, an elastic, hard, painless, and mobile mass was found anterior to the left masseter muscle. Computed tomography, magnetic resonance imaging, and ultrasonography revealed a mass in the left buccal fat pad. The lesion was identified as a benign tumor and surgical excision performed under general anesthesia. Histopathological examination revealed that the lesion was composed of a large number of vascular structures of various sizes covered with endothelial cells. Based on the clinical and histopathological findings, a diagnosis of a venous VM was made. One year has passed since the operation and no recurrence has been observed. Long-term follow-up is planned.

Three-dimensional Culture Using Atelocollagen Sponge and Self-assembling Peptide Hydrogel.

This study aimed to assess the combined application of two biomaterials, a selfassembling peptide hydrogel (SPH) and an atelocollagen sponge (ACS). The ACS was combined with SPH (PuraMatrixⓇ or PanaceaGelⓇ) and its osteogenic effects on mouse osteoblastic cell line MC3T3 then evaluated. Each type of SPH was successfully incorporated into the ACS. The MC3T3 cells showed uniform distribution within the scaffold. No necrotic cells were observed throughout the experimental procedures. When the SPH was combined with the ACS, the MC3T3 cells differentiated toward the osteo-lineage, expressing Alp, Runx2, Osx, Bsp, and Oc. PanaceaGelⓇ exhibited a stronger osteogenic effect on the cells than PuraMatrixⓇ.

Intraoral Minor Salivary Gland Tumors: A Retrospective, Clinicopathologic, Single-Center Study of 432 Cases in Japan and a Comparison with Epidemiological Data.

BACKGROUND: Intraoral minor salivary gland tumors are relatively rare lesions with histological subtypes not commonly found in major salivary glands. This study aimed to retrospectively evaluate the clinicopathologic features of intraoral minor salivary gland tumors from the Tokyo Dental College Hospital, Japan, and compare them with findings from other epidemiological studies. METHODS: We conducted a retrospective clinicopathologic evaluation of 432 cases of intraoral minor salivary gland tumors [161 male (37.3%) and 271 female (62.7%) patients; mean age: 52.5 and 48.6 years for males and females, respectively; age at diagnosis: 7-87 (mean: 50.1) years] from the Tokyo Dental College Hospital between 1975 and 2022, including 283 benign tumors (65.5%) and 149 malignant tumors (34.5%). RESULTS: The most common benign tumor was pleomorphic adenoma (n = 239), whereas mucoepidermoid carcinoma was the most common malignant tumor (n = 74). The mean age of patients with benign and malignant tumors was 48.4 and 53.2 years, respectively, with patients with malignant tumors being significantly older (P = 0.0042). The mean age of patients with malignant tumors was significantly higher in males (56.7 years) than in females (50.9 years) (P = 0.0376), although the mean age of patients with benign tumors did not differ by sex. Tumors were commonly located in the palate [250 cases (57.9%)]. Benign tumors were more frequent in the palate, upper lip, and buccal mucosa, whereas malignant tumors were more frequent in the palate, floor of the mouth, buccal mucosa, and retromolar area. CONCLUSIONS: Understanding the features of intraoral minor salivary gland tumors is useful for diagnosis. Our study provides important epidemiological data (patient differences in age at occurrence, sex, and site of origin) that will inform clinicians and researchers.

Ameloblastic carcinoma of the mandible: a case report.

BACKGROUND: Ameloblastic carcinoma is a malignant form of ameloblastoma and a very rare odontogenic tumor. We report a case of ameloblastic carcinoma that occurred after removal of a right-sided mandibular dental implant. CASE PRESENTATION: A 72-year-old female patient visited her family dentist with a complaint of pain around a lower right implant placed 37 years previously. Although the dental implant was removed with the diagnosis of peri-implantitis, the patient experienced dullness of sensation in the lower lip and was followed up by her dentist, but after no improvement. She was referred to a highly specialized institution where she was diagnosed with osteomyelitis and treated the patient with medication; however, there was no improvement. In addition, granulation was observed in the same area leading to a suspicion of malignancy, and the patient was referred to our oral cancer center. The diagnosis of squamous cell carcinoma was made after a biopsy at our hospital. Under general anesthesia, the patient underwent mandibulectomy, right-sided neck dissection, free flap reconstruction with an anterolateral thigh flap, immediate reconstruction with a metal plate, and tracheostomy. Histological analysis of the resected specimen on hematoxylin and eosin staining showed structures reminiscent of enamel pulp and squamous epithelium in the center of the tumor. The tumor cells were highly atypical, with nuclear staining, hypertrophy, irregular nuclear size, and irregular nuclear shape, all of which were suggestive of cancer. Immunohistochemical analysis showed that Ki-67 was expressed in more than 80% of the targeted area, and the final diagnosis was primary ameloblastic carcinoma. CONCLUSION: After reconstructive flap transplantation, occlusion was re-established using a maxillofacial prosthesis. The patient remained disease-free at the 1-year 3-month follow-up.

Second Primary Metachronous Malignancies Occurring in Oral Cavity of Young Adult-A Case Report.

The incidence of oral cancer in Japan is increasing. Interestingly, the number of young patients with oral cancer is also rising. A 19-year-old man with no history of smoking or drinking alcohol presented with a 20×15-mm elastic, hard, protruding mass with a white surface on the right-hand margin of the tongue. A biopsy resulted in a diagnosis of a well-differentiated squamous cell carcinoma of the tongue, for which a partial resection was subsequently performed. During regular follow-up, the patient demonstrated no clinical or imaging abnormalities until 4 years and 9 months later, when erosion was observed at the right palatoglossal arch. A malignant tumor of the right palatoglossal arch was diagnosed based on cytology and imaging findings, and total resection of the lesion performed. Histopathological examination of the resected lesion revealed a moderately differentiated squamous cell carcinoma. Epithelial dysplasia on the right-hand margin of the tongue was diagnosed 4 years and 9 months after the second surgery and was subsequently resected. The patient's condition has been favorable for 7 years since the diagnosis of the second cancer, with no noted recurrence. This case emphasizes the importance of follow-up after initial treatment, as even young people, who are likely to have to endure long-lasting consequences from treatment, can develop metachronous cancer in the oral cavity.

Role of computed tomography-based evaluation of skeletal muscle area in predicting cardiovascular outcomes in patients with chronic heart failure after cardiac resynchronization therapy.

AIM: This study aimed to determine possible associations between sarcopenia and poor cardiovascular outcomes in patients with chronic heart failure after cardiac resynchronization therapy. METHODS: This retrospective study evaluated 120 patients who underwent cardiac resynchronization therapy between March 2004 and June 2018. In total, 58 patients who underwent computed tomography within 30 days of cardiac resynchronization therapy implantation were eligible for inclusion, and their data were analyzed (25 women; 33 men; mean age 71.6 ± 8.7 years). Skeletal muscle area was measured at the third lumbar vertebra, and skeletal muscle index was calculated. Major adverse cardiovascular events included cardiovascular death, hospitalization due to heart failure, cerebral infarction, acute myocardial infarction and cardiac arrest. RESULTS: During the follow-up period (mean 868 ± 617 days), major adverse cardiovascular events occurred in 22 of 58 patients (38%). The patients were allocated to two groups according to sex-based tertiles of skeletal muscle index. The lowest tertile was defined as the low skeletal muscle index group. Kaplan-Meier survival analysis showed that the low skeletal muscle index group had a higher incidence of major adverse cardiovascular events (log-rank 4.38; P = 0.036). Cox proportional hazards regression analysis also showed that low skeletal muscle index values were significantly associated with major adverse cardiovascular events (hazard ratio 3.08; 95% confidence interval 1.26-7.66, P = 0.014). CONCLUSIONS: Decreases in skeletal mass index on computed tomography might predict the occurrence of major adverse cardiovascular events in patients with chronic heart failure who underwent cardiac resynchronization therapy. Geriatr Gerontol Int 2022; 22: 1013-1018.

Clinical investigation of patients with jaw deformity with comorbidities.

BACKGROUND: With improvements in the safety and stability of surgeries, the number of orthognathic surgeries is increasing. Most patients who undergo orthognathic surgeries are younger, and the number of orthognathic surgeries for patients with comorbidities is also increasing. We report a survey and clinical investigation of patients with comorbidities who underwent orthognathic surgeries at our department to improve the safety of orthognathic surgery. RESULTS: The participants included 296 men and 712 women, with a mean age of 28 years (13-19 years, n=144; 20-29 years, n=483; 30-39 years, n=236; 40-49 years, n=102; 50-59 years, n=39; ≥60 years, n=4). In total, 347 patients underwent one-stage Le Fort type I osteotomy and sagittal split ramus osteotomy (SSRO), 243 underwent SSRO, 287 underwent plate removal, 126 underwent genioplasty and plate removal, and five underwent other surgeries. In total, 529 patients had comorbidities (52%), including allergic diseases (n=220, 33%), respiratory diseases (n=107, 16%), neurologic and psychiatric diseases (n=69, 10%), gynecologic diseases (n=28, 4%), hematologic diseases (n=27, 4%), cardiovascular diseases (n=24, 4%), digestive diseases (n=22, 3%), metabolic and endocrine diseases (n=18, 3%), spinal diseases (n=11, 2%), ophthalmologic diseases (n=11, 2%), renal and urological diseases (n=9, 1%), and other diseases (n=117, 18%). Among the patients with comorbidities, 11 with hemorrhagic diatheses (hemophilia and von Willebrand disease), arrhythmia (atrioventricular block), psychiatric disease (adjustment disorder), and metabolic disease (diabetes) required cautious perioperative management. The patient with hemophilia was managed with regular low-dose recombinant factor VIII replacement therapy, and the patient with type I diabetes mellitus was administered continuous insulin infusion and sliding-scale insulin therapy; both patients had an uneventful course. CONCLUSIONS: The study findings suggest that with the increase in orthognathic surgeries, oral and maxillofacial surgeons should adequately manage cases requiring cautious perioperative control and highlight the importance of preoperative screening. Despite the well-established safety and postoperative stability of orthognathic surgeries, oral surgeons should adopt appropriate additional preventive measures for patients with comorbidities.

Pathological differences in the bone healing processes between tooth extraction socket and femoral fracture.

Despite various reports on the bone healing processes of tooth extraction socket and long bone fracture, the differences of pathological changes during these healing processes remain elusive. This study aims to elucidate the underlying mechanisms behind the pathophysiology of bone regeneration between the tooth extraction socket and femoral fractures through a comparative study. Eight-week-old male mice were used in the experiments. The maxillary first molar was extracted, and intramedullary nailing femoral fracture (semistabilized fracture repair) was performed in the femur. Pathological changes in these bone injuries were investigated by micro-CT, histology, immunohistochemistry, and RT-PCR until day 7 post operation. Pathological changes in drill hole injury created in cortical bone of femur were also examined. Micro-CT analyses revealed increases in mineralized tissues in both the tooth extraction socket and femoral fracture. Histological examinations revealed that tooth socket was repaired by intramembranous ossification, and intramedullary nailing femoral fracture was healed by endochondral ossification. Immunohistochemical investigation revealed that tooth socket healing associated with Sp7-positive cells but not Sox9, aggrecan, and type II collagen, while femoral fracture models exhibited positive signals for all antibodies. RT-PCR analyses revealed the expression of Sp7, Col1a1, and Col2a1 in tooth socket healing, and the expression of Sp7, Col1a1, Runx2, Sox9, Acan, Col2a1, and Col10a1 in intramedullary nailing femoral fracture. Drill hole injury was repaired primarily by intramembranous ossification when the periosteum was removed before making the hole. The present study demonstrated that the absence of cartilage appearance during tooth extraction socket healing indicates it as distinctly different pathological features from the healing processes of semistabilized femoral fracture. This study contributes to the understanding of the molecular and cellular characteristics of bone healing among the different sites of bone injury.

A clinico-statistical study of factors associated with intraoperative bleeding in orthognathic surgery.

BACKGROUND: Excessive bleeding is a major intraoperative risk associated with orthognathic surgery. This study aimed to investigate the factors involved in massive bleeding during orthognathic surgeries so that safe surgeries can be performed. Patients (n=213) diagnosed with jaw deformities and treated with bimaxillary orthognathic surgery (Le Fort I osteotomy and bilateral sagittal split ramus osteotomy) in the Department of Oral and Maxillofacial Surgery at the Suidobashi Hospital, Tokyo Dental College between January 2014 and December 2016 were included. Using the patients' medical and operative records, the number of cases according to sex, age at the time of surgery, body mass index (BMI), circulating blood volume, diagnosis of maxillary deformity, direction of maxillary movement, operative duration, incidence of bad split, injury of nasal mucosa, and blood type were analyzed. RESULTS: The results revealed that BMI, circulating blood volume, nasal mucosal injury, and operative time were associated with the risk of intraoperative massive bleeding in orthognathic surgeries. Chi-square tests and binomial logistic regression analyses showed significant differences in BMI, circulating blood volume, direction of maxillary movement, operative duration, and injury to the nasal mucosa. Operative duration emerged as the most important risk factor. Furthermore, a >4-mm upward migration of the posterior nasal spine predicted the risk of massive bleeding in orthognathic surgery. CONCLUSIONS: The upward movement of the maxilla should be recognized during the preoperative planning stage as a risk factor for intraoperative bleeding, and avoiding damage to the nasal mucosa should be considered a requirement for surgeons to prevent massive bleeding during surgery.

Bone regeneration of induced pluripotent stem cells derived from peripheral blood cells in collagen sponge scaffolds.

OBJECTIVE: Stem cell-based regeneration therapy offers new therapeutic options for patients with bone defects because of significant advances in stem cell research. Although bone marrow mesenchymal stem cells are the ideal material for bone regeneration therapy using stem cell, they are difficult to obtain. Induced pluripotent stem cells (iPSCs) are now considered an attractive tool in bone tissue engineering. Recently, the efficiency of establishing iPSCs has been improved by the use of the Sendai virus vector, and it has become easier to establish iPSCs from several type of somatic cells. In our previous study, we reported a method to purify osteogenic cells from iPSCs.This study aimed to evaluate the osteogenic ability of iPSCs derived from peripheral blood cells. METHODOLOGY: Mononuclear cells (MNCs) were obtained from human peripheral blood. Subsequently, T cells were selectively obtained from these MNCs and iPSCs were established using Sendai virus vectors. Established iPSCs were evaluated by the expression of undifferentiated markers and teratoma formation assays. Osteoblasts were induced from these iPSCs and evaluated by the expression of osteoblast markers. Additionally, the induced osteoblasts were transplanted into rat critical size calvaria bone defect models with collagen sponge scaffolds. Samples were evaluated by radiographical and histological assessments. RESULTS: Induced osteoblasts expressed several osteoblast-specific markers. The results of radiographical and histological assessments revealed that the cell transplant group had bone formations superior to those of the control group. CONCLUSIONS: This study suggests that peripheral blood MNCs have the potential to differentiate into osteoblasts. Although there are some hurdles in iPSC transplantation, osteoblasts obtained from MNC-iPSCs could be applied to bone regeneration therapy in the future.

Osteotomy training for dental students using three-dimensional simulation software and maxillofacial three-dimensional-printed models.

PURPOSE/OBJECTIVES: Simulated educational models of teeth, bones, and gums have been used for a long time in procedural skills training in dentistry.  The advent of three-dimensional (3D) printing technologies and additive manufacturing has facilitated the production of more advanced 3D printed models that can be utilized for surgical and dental training together with other technologies (e.g., 3D scanners and image analysis software). METHODS: We conducted training on osteotomy in the maxilla and mandible using maxillofacial simulation software (MSS) and a 3D-printed model for 5th-year undergraduate dental students (13 students in 2017 and 11 students in 2018 with more than half of their results). We compared the group (13 students) who performed osteotomy after participating in the simulation lecture with those (11 students) who performed osteotomy after performing self-simulation (they were instructed to bring their personal computers and install the MSS) using tests and questionnaires (pre- and post-curriculum). RESULTS: The average test score was significantly higher in the group who performed osteotomy using the 3D-printed model after performing self-simulation; participants in this group had acquired a better understanding of the surgical procedure. Comparison using questionnaires showed a significant difference in the students' understanding of instruments and surgical techniques between both groups. CONCLUSION: The MSS and 3D printed models are widely used clinically. Incorporating these in the curriculum will help accelerate student development. In addition, prompt education on the purpose and usefulness of these tools will not only facilitate simulation software and 3D-printed model-based treatment plan in the clinic but also promote further research.