Efficacy of CHA2DS2-VASc scores in predicting chronic kidney disease risk in patients treated in cardiac intensive care units.

The CHA2DS2 -VASc score is a vital clinical tool for evaluating thromboembolic risk in patients with atrial fibrillation (AF). This study investigated the efficacy of the CHA2DS2 -VASc score in a cohort of 737 heterogeneous patients (mean age: 63 years) receiving care in cardiac intensive care units (CICUs), with a creatinine-based estimated glomerular filtration rate (eGFR) of ≥60 mL/min/1.73 m2 upon admission and discharge. Incident chronic kidney disease (CKD) was defined as the emergence of a new-onset eGFR<60 mL/min/1.73 m2, accompanied by a decline of >5 mL/min/1.73 m2 compared to that at discharge. The primary endpoint was the incidence of CKD, and the secondary endpoints included all-cause mortality, cardiovascular events, and progression to end-stage kidney disease. In this cohort, 210 (28 %) patients developed CKD. Multivariate analyses revealed that CHA2DS2 -VASc score was a significant independent predictor of incident CKD, regardless of the presence of AF. Integration of CHA2DS2 -VASc scores with eGFR enhanced the predictive accuracy of incident CKD, as evidenced by the improved C-index, net reclassification improvement, and integrated discrimination improvement values (all p < 0.05). Over the 12-month follow-up period, a composite endpoint was observed in 61 patients (8.3 %), with elevated CHA2DS2 -VASc scores being independently associated with this endpoint. In conclusion, CHA2DS2-VASc scores have emerged as robust predictors of both CKD incidence and adverse outcomes. Their inclusion substantially refined the 12-month risk stratification of patients with preserved renal function hospitalized in the CICUs.

Inhalation of gaseous hypochlorous acid and its effect on human respiratory epithelial cells in laboratory model systems.

During the disinfection of indoor spaces using gaseous hypochlorous acid (HOCl(g)), inhalation is the most common route of exposure for humans. In this study, an artificial human respiratory tract model was exposed to 12-140 ppb HOCl(g) at an aspiration flow rate of 800 mL/s for 15 h in a 1 m3 chamber. The respiratory tract model was equipped with 5th order bronchi and all gas-contact parts were made of silicone rubber with no other chlorine-consuming substances. The concentration of HOCl(g) reaching the lung pseudo-space was approximately 47.4% of the HOCl(g) concentrations in the chamber and was calculated to be very close to zero when the chamber concentration was less than 20.5 ppb. The disappearance of HOCl(g) during inhalation is likely due to the adsorption of HOCl(g) on the gas-contact silicone rubber surfaces. The cytotoxicity of HOCl(g) on respiratory epithelial cells was also examined using human air-liquid-interface airway tissue models. Human nasal epithelium and bronchiolar epithelium were exposed to 100 ppb and 500 ppb HOCl(g) for 8 h and 5 d, respectively. No significant effects of HOCl(g) on cell viability and ciliary activity were observed in any cell type, indicating that low concentrations of HOCl(g）, less than 500 ppb, had no cytotoxic effect.

Revisiting the History of Odontoma, with Special Reference to Its Original Illustration.

BACKGROUND: Practically every facet of the most common odontogenic tumor, odontoma, has been covered by an extensive volume of literature. However, uncertainty about its precise history has persisted. MATERIALS AND METHODS: The historical evolution of odontoma was traced with reference to the original illustrations that accompanied European and American reports published at the beginning of the 19th century and also at the turn of the century. RESULTS: The prevailing views regarding the first description of odontoma by Oudet of Paris in 1809 and the original designation "odontome" by Broca of Paris in 1867 are not entirely accurate. Before Broca's suggested term, "exostose dentaire" (dental exostosis) and "tumeur dentaire" (dental tumor) proposed by Oudet and Forget of Paris, respectively, were popular terms adopted in France, while in Briatin the terms "warty tooth" and "supernumerary teeth" proposed by Salter and Tomes of London, respectively, were widely coined. The original illustrations of complex odontoma were published by Wedl of Vienna in 1851, and in 1862 Tomes published the first drawing of compound odontoma denticles. Before the advent of diagnostic radiography in the early 1900s, spontaneous exposure or eruption of odontoma followed by secondary infection was very common. In 1887-1888, Bland Sutton of London criticized Broca's monumental research and formulated the first modern classification which, in essence, remains valid today. At that time, large osteomas of the maxilla were inappropriately classified as odontomas by many pathologists because of Bland Sutton's influential view. Interestingly, the first radiographic evidence of odontoma was published by the American oral surgeon Gilmer in 1899. CONCLUSION: In view of their fundamental achievements, the names of Wedl, Salter, Broca and Bland Sutton have been closely associated with the true history of odontoma.

Warthin Tumor of the Parotid Gland: The History of an Eponym.

The eponymous history of Warthin tumor (WT) is a fascinating issue in the field of salivary gland pathology. The late decades of the nineteenth century and the turn of the century saw notable German and French contributions on WT. Especially, the seminal 1910 paper of Albrecht and Arzt of Vienna is the foundation for the current knowledge of WT. It is generally believed that prior to this pioneering study, Hildebrand of Göttingen accurately described the lesion of WT in 1895. However, the historical origins of WT appear to be unsettled, and only a few German pathologists and surgeons are aware that dating back to 1885, the first recognizable reference to WT was that by the renowned German-Swiss pathologist Zahn, whose name is eponymously associated with "Zahn infarct" and "lines of Zahn". Two noted French surgeons with a major interest in pathology, Albarrán in 1885 and Lecéne in 1908, did not contribute to the topic. Since the 1950s, a mostly American group of pathologists and surgeons gradually adopted the term WT to replace the very accurate histologic descriptor "papillary cystadenoma lymphomatosum" coined by Warthin himself in 1929. It is our opinion that from a historical viewpoint, there is no particular reason why this tumor should have been named WT.

The True History of Cementoblastoma.

REVIEW OF THE LITERATURE: Cementoblastoma (CB) is unique among odontogenic tumors because its gross pathological anatomy is pathognomonic in most cases, i.e., a rounded calcified growth that is fused to the root of a tooth and completely encapsulated by fibrous tissue. The resulting radiographic appearance is a well-defined, globular mixed radiopaque/lucent or completely radiopaque mass obliterating some details of the root, with a thin radiolucent zone surrounding the central opacity. Although hundreds of publications have covered the clinicopathologic features of CB, almost nothing is known about its true history. Also it seems there is little understanding about how the term "CB" was originally introduced as a pathologic entity. This report covers some overlooked papers on CB dating back to the 19th century, including the first complete description in 1888 and the first radiographic presentation in 1906.

Clinical expert consensus document on drug-coated balloon for coronary artery disease from the Japanese Association of Cardiovascular Intervention and Therapeutics.

Drug-coated balloon (DCB) technology was developed to deliver the antiproliferative drugs to the vessel wall without leaving any permanent prosthesis or durable polymers. The absence of foreign material can reduce the risk of very late stent failure, improve the ability to perform bypass-graft surgery, and reduce the need for long-term dual antiplatelet therapy, potentially reducing associated bleeding complications. The DCB technology, like the bioresorbable scaffolds, is expected to be a therapeutic approach that facilitates the "leave nothing behind" strategy. Although newer generation drug-eluting stents are the most common therapeutic strategy in modern percutaneous coronary interventions, the use of DCB is steadily increasing in Japan. Currently, the DCB is only indicated for treatment of in-stent restenosis or small vessel lesions (< 3.0 mm), but potential expansion for larger vessels (≥ 3.0 mm) may hasten its use in a wider range of lesions or patients with obstructive coronary artery disease. The task force of the Japanese Association of Cardiovascular Intervention and Therapeutics (CVIT) was convened to describe the expert consensus on DCBs. This document aims to summarize its concept, current clinical evidence, possible indications, technical considerations, and future perspectives.

Recurrent mitral regurgitation with haemolytic anaemia after MitraClip procedure: an autopsy case report.

Background: Transcatheter edge-to-edge mitral valve repair (TMVr) has been developed as an alternative therapeutic approach to patients with severe mitral regurgitation (MR) at high-surgical risks. Single leaflet device attachment (SLDA) is a well-known complication after the TMVr procedure, while an autopsy case experiencing haemolytic anaemia has been scarcely reported. Case summary: A 79-year-old woman presented with New York Heart Association Class 3 congestive heart failure due to severe MR. The Heart Team planned TMVr using the MitraClip considering a high-surgical risk due to the history of open-chest surgery. The procedure was successful with two clips and a significant reduction of MR was confirmed. On the 12th day after the procedure, congestive heart failure was worsened and a transthoracic echocardiogram revealed severe MR suggestive of SLDA. Blood test showed normocytic anaemia with serum lactate dehydrogenase level elevation and renal function deterioration. We diagnosed as mechanical haemolysis induced by recurrent MR because of a decrease in serum haptoglobin level and the presence of schizocyte in the blood smear. Despite our intensive medical treatment, she died on the 119th day after the procedure. The pathological autopsy demonstrated that the ruptured leaflet was thickened with layered structure and severe fibrosis, while there were no findings of calcification, vegetations, or abscesses. Discussion: Single leaflet device attachment and subsequent mechanical haemolysis are rare but fatal complications after TMVr with the MitraClip. Not only degenerative MR but also functional MR may be associated with valve leaflet degeneration. A possibility of mechanical haemolysis should be considered when recurrent MR is observed after TMVr.

Hypoplasia of medial pterygoid process in sphenoid bone relates to decreased mesenchymal cell proliferation in the Runx2-haploinsufficient cleidocranial dysplasia mouse model.

OBJECTIVE: Hypoplasia of the medial pterygoid process of the sphenoid bone is a distinct skeletal phenotype in runt-related transcription factor 2 (Runx2) heterozygous mice and patients with cleidocranial dysplasia. The aim of this study was to investigate the involvement of Runx2 in hypoplasia by regulating cell proliferation in the mesenchymal cell condensation region. DESIGN: A total of thirty mouse embryos were used. The medial pterygoid process region in the Runx2+/+, Runx2+/-, and Runx2-/- mouse embryos were histologically investigated. Immunohistochemistry for Runx2 and proliferating cell nuclear antigen (PCNA) was carried out. RESULTS: In embryonic day 14.5, mesenchymal cell condensation appeared at the future medial pterygoid process in Runx2+/+ mice, but was obscure in Runx2+/- mice. In these areas, cells showed a dual expression of Runx2 and PCNA in both Runx2+/+ and Runx2+/- mice. However, the number of Runx2- and PCNA-positive cells was decreased in Runx2+/- mice. In Runx2-/- mice, mesenchymal cell condensation appeared on embryonic day 18.5 at the medial pterygoid process region, associated with a few PCNA-positive cells. Moreover, the PCNA-positive cell rate in the medial pterygoid process was significantly lower in Runx2-/- mice than in Runx2+/+ and Runx2+/- mice. On embryonic day 18.5, Runx2+/- and Runx2-/- mice showed significantly shorter axial length of medial pterygoid process compared to that in Runx2+/+ mice. CONCLUSIONS: The present study demonstrates that Runx2 is involved in cell proliferation in the mesenchymal cell condensation region of the medial pterygoid process during mouse embryonic development.

Emergence of Hepatitis C Virus Genotype 2c Infection Among Human Immunodeficiency Virus-Infected Men Who Have Sex With Men in Tokyo, Japan.

ABSTRACT: We report on hepatitis C virus genotype 2c infection in 12 human immunodeficiency virus-infected men who have sex with men in Tokyo, Japan. The uncommon strains from the 12 patients were genetically clustered; they suggested an emerging outbreak in this population at high risk of sexually transmitted infections.

Activation of Wnt signalling reduces the population of cancer stem cells in ameloblastoma.

OBJECTIVES: The treatment of ameloblastoma, an odontogenic epithelial tumour destroying jawbone, mainly depends on radical destructive resections. Other therapeutic options are limited by the characteristics of ameloblastoma, such as high recurrence rates and resistance to radiation and chemotherapy, which implies possible existence of cancer stem cells (CSCs) in ameloblastoma. Here, we identified a putative CSC population in immortalized and primary human ameloblastoma cells and examined possible therapeutic reagents to reduce the CSC population. METHODS: We investigated subpopulations of AM-1 cell line and human ameloblastoma cells using immunocytochemistry and flow cytometry and the effects of Wnt signalling activators on the 2- and 3-dimensional cultured ameloblastoma cells using molecular biological analyses. RESULT: Among heterogenous ameloblastoma cells, small-sized and round-shaped cells were found to be proliferative and expressed a marker of dental epithelial stem cells, SRY-box 2 (Sox2). Exogenous activation of Wnt signalling using glycogen synthase kinase 3ß inhibitors, lithium chloride (LiCl) and valproic acid (VPA), increased the cell size and decreased proliferation of cells and expression of Sox2 in 2 dimensionally cultured AM-1 and human primary ameloblastoma cells. Furthermore, the growth of 3 dimensionally cultured AM-1 cells as suspended or embedded in gel was suppressed by treatment with Wnt signalling activators, VPA and CHIR99021, or antibodies to sclerostin, an antagonist of Wnt signalling. CONCLUSION: We suggest that Wnt signalling activators are potential drug candidates to suppress CSCs in ameloblastoma.

The Advent of Studies on Jaw Cysts with Keratinization: A Review of Overlooked Papers on Odontogenic Keratocyst and Orthokeratinized Odontogenic Cyst.

Previous reports of odontogenic keratocyst (OKC) and orthokeratinized odontogenic cyst (OOC) with coverage of the old literature have tended to overlook the underlying theme of the first description. From a historical viewpoint, a French paper "kyste butyreux du sinus maxillaire simulant un cancer encéphaloid" published in 1855 by Maisonneuve popularized the notion of so-called "buttery cyst", which ultimately became known as jaw cyst with a keratinized lining. Soon after in 1856, Nélaton presented a case of OKC at the Anatomical Society of Paris, but his brief communication provided little information about its histopathology. It was Mikulicz who conducted, in 1876, a pioneering descriptive pathological study of OKC. In 1886, 10 years after Mikulicz's German report, OOC was first described in detail by Jeannel of Toulouse. The mid to late decades of the nineteenth century saw notable European contributions on the topic.

Long-term administration of pegylated liposomal doxorubicin at almost twice the recommended lifetime dose in 10 years without cardiotoxicity in a Japanese patient with HIV-associated Kaposi sarcoma.

We report a Japanese patient with HIV-associated Kaposi sarcoma (KS) who had many cutaneous KS lesions with extensive bilateral groin edema. As the KS was refractory to antiretroviral therapy and pegylated liposomal doxorubicin (PLD), he was administered PLD up to a cumulative dose of 940 mg/m2 in 10 years, which exceeded the recommended lifetime dose (550 mg/m2). However, the patient showed no major adverse events, including cardiotoxicity, and he eventually died of pancreatic cancer.

Sphenoid bone hypoplasia is a skeletal phenotype of cleidocranial dysplasia in a mouse model and patients.

Cleidocranial dysplasia (CCD) is an autosomal dominant disorder caused by heterozygous mutations in RUNX2. Affected individuals exhibit delayed maturation or hypoplasia in various bones, mainly including those formed by intramembranous ossification. Although several reports described deformation of the sphenoid bone in CCD patients, details of the associated changes have not been well documented. Most parts of the sphenoid bone are formed by endochondral ossification; however, the medial pterygoid process is formed by intramembranous ossification associated with secondary cartilage. We first investigated histological changes in the medial pterygoid process during different developmental stages in Runx2+/+ and Runx2+/- mice, finding that mesenchymal cell condensation of the anlage of this structure was delayed in Runx2+/- mice as compared with that in Runx2+/+ mice. Additionally, in Runx2+/+ mice, Osterix-positive osteoblastic cells appeared at the upper region of the anlage of the medial pterygoid process, and bone trabeculae appeared to associate with subsequent secondary cartilage formation. By contrast, few Osterix-positive osteoblastic cells appeared at the upper region of the anlage of the medial pterygoid process, and no bone trabeculae appeared thereafter in Runx2+/- mice. At more advanced embryonic stages, endochondral ossification occurred at the lower part of the medial pterygoid process in both Runx2+/+ and Runx2+/- mice. After birth, well-developed bone trabeculae occupied two-thirds of the cranial side of the medial pterygoid process, and cartilage appeared beneath these bones in Runx2+/+ mice, whereas thin trabecular bone appeared at the center of the cartilage of the medial pterygoid process in Runx2+/- mice. In adult mice, the body and medial pterygoid processes of the sphenoid bone comprised mature bones in both Runx2+/+ and Runx2+/- mice, although the axial length of the medial pterygoid processes was apparently lower in Runx2+/-mice as compared with that in Runx2+/+mice based on histological and micro-computed tomography (CT) examinations. Moreover, medical-CT examination revealed that in CCD patients, the medial pterygoid process of sphenoid bone was significantly shorter relative to that in healthy young adults. These results demonstrated that the medial pterygoid process of the sphenoid bone specifically exhibited hypoplasia in CCD.

Bone-Targeted Alkaline Phosphatase Treatment of Mandibular Bone and Teeth in Lethal Hypophosphatasia via an scAAV8 Vector.

Hypophosphatasia is an inherited disease caused by mutations in the gene encoding tissue-nonspecific alkaline phosphatase (TNALP), the major symptom of which is hypomineralization of the bones and teeth. We had recently demonstrated that TNALP-deficient (Akp2-/- ) mice, which mimic the phenotype of the severe infantile form of hypophosphatasia, can be treated by intramuscular injection of a self-complementary (sc) type 8 recombinant adeno-associated virus (rAAV8) vector expressing bone-targeted TNALP with deca-aspartates at the C terminus (TNALP-D10) via the muscle creatine kinase (MCK) promoter. In this study, we focused on the efficacy of this scAAV8-MCK-TNALP-D10 treatment on the mandibular bone and teeth in neonatal Akp2-/- mice. Upon scAAV8-MCK-TNALP-D10 injection, an improvement of mandibular growth was observed by X-ray analysis. Micro-computed tomography analysis revealed progressive mineralization of the molar root in the treated Akp2-/- mice, and morphometric parameters of the alveolar bone were improved. These results suggest that the mandibular bones and teeth of hypophosphatasia were effectively treated by muscle directed rAAV-mediated TNALP-D10 transduction. Our strategy would be promising for future hypophosphatasia gene therapy because it induces dentoalveolar mineralization and reduces the risk of tooth exfoliation.