Usefulness of Oral Xa Inhibitor for Management of Ischemic Stroke Associated with Thrombosis in the Pulmonary Vein Stump after Lung Resection.

OBJECTIVES: Brain infarction is a critical complication after lung resection using video-assisted thoracoscopic surgery. Recent reports have described its association with thrombosis in the pulmonary vein (PV) stump. However, the optimal management of this complication remains controversial. We describe serial 3 cases of brain infarctions associated with thrombosis in the PV stumps, which were successfully treated with the oral Xa inhibitor rivaroxaban. METHODS AND RESULTS: We retrospectively reviewed medical records of 3 patients. The first case was a 72-year-old man who underwent left upper lobectomy for treatment of lung adenocarcinoma. The second case was a 55-year-old man who underwent right lower segmentectomy for treatment of metastatic tumor from Barrett's esophageal carcinoma. The third case was a 73-year-old man who underwent left upper lobectomy for treatment of metastatic tumor from colon adenocarcinoma. In the first case, a large cerebellar infarction was developed and a decompressive craniotomy was performed on postoperative day 4. In the second and the third case, cerebral infarctions in the territories of right middle cerebral arteries occurred on postoperative day 2. In all cases, contrast-enhanced computed tomography demonstrated the thrombi in the stumps of the PVs. They were treated with oral administration of rivaroxaban without adverse effect, and the thrombi in the PVs disappeared within 1 month. DISCUSSION: Blood flow stasis in the long PV stump after lung resection might contribute to thrombosis development. Oral Xa inhibitor rivaroxaban appeared to be safe and useful for the management of ischemic stroke associated with PV thrombosis after lung resection.

Free testosterone concentration is inversely associated with markers of liver fibrosis in men with type 2 diabetes mellitus.

The association between serum testosterone level and liver fibrosis in patients with non-alcoholic fatty liver disease is unclear. To clarify this association, we investigated the relationship between serum free testosterone concentration and markers of liver fibrosis in men with type 2 diabetes mellitus but no obvious features of alcohol consumption. This retrospective observational cross-sectional study enrolled 248 men with type 2 diabetes mellitus. The FIB-4 index was measured as a marker of liver fibrosis, and multiple linear regression analysis was performed to examine its association with serum free testosterone concentration. In addition, the 7S domain of type IV collagen (IV-7S) was examined in 140 of the 248 patients. The mean free testosterone concentration was 10.6 ± 6.8 pg/mL and the means of the FIB-4 index and IV-7S were 1.64 ± 1.19 and 4.02 ± 1.11 ng/mL, respectively. After adjusting for all relevant variables, serum free testosterone concentrations were inversely associated with both the FIB-4 index and IV-7S (ß; -0.28, P < 0.0001, and ß; -0.28, P = 0.002, respectively). Measuring serum free testosterone concentrations in men with type 2 diabetes mellitus may help to predict progression to advanced liver disease. Identifying patients at risk may help to prevent the development of cirrhosis and hepatocellular carcinoma.

Multicenter phase II study of an oral care program for patients with head and neck cancer receiving chemoradiotherapy.

PURPOSE: This multicenter phase II trial assessed the clinical benefit of a multidisciplinary oral care program in reducing the incidence of severe chemoradiotherapy-induced oral mucositis (OM). METHODS: Patients with head and neck cancer (HNC) who were scheduled to receive definitive or postoperative chemoradiotherapy were enrolled. The oral care program included routine oral screening by dentists and a leaflet containing instructions regarding oral care, nutrition, and lifestyle. Oral hygiene and oral care were evaluated continuously during and after the course of chemoradiotherapy. The primary endpoint was the incidence of grade ≥3 OM assessed by certified medical staff according to the Common Terminology Criteria of Adverse Events version 3.0. RESULTS: From April 2012 to December 2013, 120 patients with HNC were enrolled. Sixty-four patients (53.3 %) developed grade ≥3 OM (i.e., functional/symptomatic). The incidence of grade ≤1 OM at 2 and 4 weeks after radiotherapy completion was 34.2 and 67.6 %, respectively. Clinical examination revealed that 51 patients (42.5 %) developed grade ≥3 OM during chemoradiotherapy. The incidence of grade ≤1 OM at 2 and 4 weeks after radiotherapy completion was 54.7 and 89.2 %, respectively. The incidences of grade 3 infection and pneumonitis throughout chemoradiotherapy were <5 %. Only 6.7 % of patients had unplanned breaks in radiotherapy, and 99.2 % completed treatment. CONCLUSIONS: A systematic oral care program alone is insufficient to decrease the incidence of severe OM in patients with HNC being treated with chemoradiotherapy. However, systematic oral care programs may indirectly improve treatment compliance by decreasing infection risk. TRIAL REGISTRATION NUMBER: UMIN000006660.

A 10-year experience of totally extraperitoneal endoscopic repair for adult inguinal hernia.

PURPOSE: Laparoscopic surgery is fast becoming the treatment of choice for inguinal hernia. By reviewing our 10-year experience of performing totally extraperitoneal repair (TEP), we sought to establish its clinical significance in the treatment of adult inguinal hernia. METHODS: We reviewed retrospectively the clinical records of patients who underwent TEP for adult inguinal hernia between January 2003 and December 2012. RESULTS: None of the 303 patients with adult primary or recurrent inguinal hernia in our study needed TEP converted to other procedures or suffered serious complications during the procedure. A significant difference was noted in the operation time between direct (n = 32) vs indirect (n = 128) hernias in the primary unilateral inguinal hernia group (91 ± 27 vs 80 ± 32 min, p = 0.033) and between direct/direct (n = 31) vs indirect/indirect (n = 24) hernias (136 ± 58 vs 89 ± 24 min, p = 0.01) in the primary bilateral inguinal hernia group. The only postoperative complications recorded were four cases of hernia recurrence (1.3 %) and one case of chronic pain (0.3 %). CONCLUSIONS: The results obtained for TEP over 10 years support this as a promising procedure for the treatment of adult inguinal hernia.

Primary carcinoid tumor in a retroperitoneal mature teratoma: report of a case.

Primary retroperitoneal teratoma in an adult is rare, as is the occurrence of a malignant tumor within a mature teratoma, known as "malignant transformation". A 24-year-old woman was admitted to our hospital for investigation of an abdominal mass. Computed tomography and magnetic resonance imaging revealed a multilocular mass in the right upper abdomen. The tumor consisted of fat, soft tissue, and bone, with a slightly enhanced solid component. The tumor was diagnosed preoperatively as a retroperitoneal mature teratoma with an immature component, and excised. Histologically, it was composed mainly of mature fat, soft tissue, and bone, accompanied by a solid component of prostate-like tissue. In addition, a latent carcinoid tumor was recognized in the middle of the tumor. The tumor was finally diagnosed as a primary carcinoid tumor within the retroperitoneal mature teratoma. The patient has been followed-up for 24 months since her operation without any evidence of recurrence. We report this case to highlight the possibility of malignant transformation in adult retroperitoneal teratoma, even when the preoperative diagnosis is benign mature teratoma.

Changes in oral microflora following 0.3% cetylpyridinium chloride-containing mouth spray intervention in adult volunteers after professional oral care: Randomized clinical study.

OBJECTIVES: This study explored the changes in bacterial flora composition and total bacterial count in the saliva and tongue coating, along with the change in the tongue coating index (TCI) following an intervention with 0.3% cetylpyridinium chloride (CPC) mouth spray after professional oral care. MATERIALS AND METHODS: Fifty-two adult volunteers aged 30-60 years were equally divided into CPC spray (n = 26) and control (n = 26) groups. All subjects underwent scaling and polishing. The CPC spray group was administered four puffs of CPC spray to the tongue dorsum four times a day for 3 weeks. The control group performed only routine daily oral care (brushing) and did not use any other spray. Bacteriological evaluation of saliva and tongue coating was performed using 16S ribosomal RNA gene sequencing and quantitative polymerase chain reaction. The tongue coating was evaluated to calculate the TCI. A per-protocol analysis was conducted for 44 subjects (CPC spray group, n = 23; control group, n = 21). RESULTS: At 1 and 3 weeks after CPC spray use, the flora of the saliva and tongue coating changed; the genus Haemophilus was dominant in the CPC spray group, whereas the genus Saccharibacteria was dominant in the control group. The sampling time differed among individual participants, which may have affected the bacterial counts. There was no significant intragroup change in TCI in either group. CONCLUSIONS: CPC spray affected the bacterial flora in the saliva and tongue coating, particularly with respect to an increase in the abundance of Haemophilus. However, CPC spray did not change the TCI. These results suggest that it may be optimal to combine CPC spray with a physical cleaning method such as using a tongue brush or scraper. Clinical Trial Registration: University Hospital Medical Information Network UMIN000041140.

Protective effects of polysaccharides and polyhydric alcohols in a dry mouth model in cultured cells.

PURPOSE: The goal of the study was to investigate the effects of 21 polysaccharides and 12 polyhydric alcohols on inhibition of dryness in oral mucosal epithelial cells in vitro. All the tested compounds are currently used in oral products. METHODS: Human gingival epithelial Ca9-22 cells were incubated in 96-well plates until the cells reached confluence. After removal of the culture medium, the cells were incubated with a solution containing one of 21 polysaccharides (seven semisynthetic and 14 natural polysaccharides) or 12 polyhydric alcohols for 15 min (short-term treatment). After removal of the sample solution, the cells were dried at 25°C and 30% humidity, and cell viability was measured to determine the effect of each compound on prevention of cell death due to drying. The effects of the polyhydric alcohols were also examined for 3 days (long-term treatment). RESULTS: The semisynthetic polysaccharides ethylcellulose (EC), methylcellulose (MC), and hydroxypropylmethylcellulose (HPMC) and the natural polysaccharides xanthan and gellan gum significantly inhibited cell death due to drying. Hydroxypropylcellulose increased cell death under these conditions. Of the polyhydric alcohols, long-term treatment with glycosyltrehalose significantly inhibited cell death due to drying, but short-term treatment with glycosyltrehalose did not do so. Long-term treatment had an effect on cell proliferation that appeared to differ from the effect of short-term treatment. CONCLUSIONS: Short-term treatment with EC, MC, HPMC, xanthan gum, and gellan gum and long-term treatment with glycosyltrehalose showed significant inhibition of cell death due to drying. These materials might have protective effects against dry mouth.

Genetic Homology between Bacteria Isolated from Pulmonary Abscesses or Pyothorax and Bacteria from the Oral Cavity.

Pulmonary abscesses and pyothorax are bacterial infections believed to be caused primarily by oral microbes. However, past reports addressing such infections have not provided genetic evidence and lack accuracy, as they used samples that had passed through the oral cavity. The aim of this study was to determine whether genetically identical bacterial strains exist in both the oral microbiota and pus specimens that were obtained percutaneously from pulmonary abscesses and pyothorax, without oral contamination. First, bacteria isolated from pus were identified by 16S rRNA gene sequencing. It was then determined by quantitative PCR using bacterial-species-specific primers that DNA extracted from paired patient oral swab sample suspensions contained the same species. This demonstrated sufficient levels of bacterial DNA of the targeted species to use for further analysis in 8 of 31 strains. Therefore, the whole-genome sequences of these eight strains were subsequently determined and compared against an open database of the same species. Five strain-specific primers were synthesized for each of the eight strains. DNA extracted from the paired oral swab sample suspensions of the corresponding patients was PCR amplified using five strain-specific primers. The results provided strong evidence that certain pus-derived bacterial strains were of oral origin. Furthermore, this two-step identification process provides a novel method that will contribute to the study of certain pathogens of the microbiota. IMPORTANCE We present direct genetic evidence that some of the bacteria in pulmonary abscesses and pyothorax are derived from the oral flora. This is the first report describing the presence of genetically homologous strains both in pus from pulmonary abscesses and pyothorax and in swab samples from the mouth. We developed a new method incorporating quantitative PCR and next-generation sequencing and successfully prevented contamination of pus specimens with oral bacteria by percutaneous sample collection. The new genetic method would be useful for enabling investigations on other miscellaneous flora; for example, detection of pathogens from the intestinal flora at the strain level.

Effects of Diluents, Saliva and Other Organics on the Microbicidal Activity of Cetylpyridinium Chloride and Povidone-iodine.

Povidone-iodine (PVP-I) is used for infection control and preoperative sterilization of the oral and pharyngeal regions. Marketed preparations containing cetylpyridinium chloride (CPC) are used to inhibit growth of oral bacteria. We conducted an in vitro study of the sterilizing effects of these microbicides on 10 oral bacterial strains and fungi related to pneumonia and periodontal disease, after dilution with phosphate-buffered saline (PBS), saliva, and components in saliva. The CPC solution was evaluated at 50 mg/100 mL, which is the concentration used in products. CPC sterilized all strains within 1 minute. Prolongation of the sterilization time associated with dilution was more gradual in comparison to PVP-I solution. CPC sterilized 7 of 10 microbial strains within 3 minutes at 3 mg/100 mL. At 500 mg/100 mL, which is near the upper limit of the concentration that is actually used, PVP-I solution sterilized 7 microbial strains within 3 minutes. However, PVP-I had no sterilization effect when diluted to 100 mg/100 mL or lower. With addition of saliva, PVP-I sterilized 2 microbial strains within 3 minutes at 500 mg/100 mL, whereas CPC solution sterilized 9 microbial strains within 1 minute at 50 mg/100 mL. Our results show that in use influenced by dilution with saliva, CPC is likely to maintain a strong sterilization effect, whereas PVP-I may have a reduced effect.

Applying deep artificial neural network approach to maxillofacial prostheses coloration.

PURPOSE: Maxillofacial prosthetic rehabilitation replaces missing structures to recover the function and aesthetics relating to facial defects or injuries. Deep learning is rapidly expanding with respect to applications in medical fields. In this study, we apply the artificial neural network (ANN)-based deep learning approach to coloration support for fabricating maxillofacial prostheses. METHODS: We compared two machine learning algorithms, ANN-based deep learning and the random forest algorithm, to determine the compounding amount of pigment. We prepared 52 silicone elastomer specimens of varying colors and measured the CIE 1976 L* a* b* color space information using a spectrophotometer on the input dataset. The output of these algorithms indicated the compounding amount of four pigments. According to the algorithms' pigment compounding predictions, we prepared the specimens for validation analysis and measured the CIE 1976 L* a* b* values. We determined the color differences between the real skin color of five research participants (22.3 ± 1.7 years) and that of the silicone elastomer specimens fabricated based on the algorithm predictions using the CIEDE00 ΔE00 color system. RESULTS: The color differences (ΔE00 value) between the real skin color and silicone elastomer validation specimens were 3.45 ± 0.87 (ANN) and 5.54 ± 1.41 (random forest), which indicates that the deep ANN approach produced superior results with respect to the ΔE00 value compared with the random forest algorithm. CONCLUSIONS: These results suggest that applying deep ANN is a promising technique for the coloration of maxillofacial prostheses.

Identification and Modification of Porphyromonas gingivalis Cysteine Protease, Gingipain, Ideal for Screening Periodontitis.

Chronic periodontitis is an inflammatory disease caused by the formation of oral microbial biofilms. Periodontitis is associated with general health and not only oral diseases. Porphyromonas gingivalis is a well-known keystone pathogen for periodontitis and is associated with several systemic diseases, such as diabetes mellitus and Alzheimer's disease. We previously developed a system for screening periodontitis using P. gingivalis-specific serum immunoglobulin G (IgG) in an enzyme-linked immunosorbent assay with a sensitivity of 0.774 and a specificity of 0.586 and an area under the receiver operating characteristic curve of 0.708. However, the antigens elicited non-specific responses, since they were obtained from whole extracts of sonicated cultured bacteria. The purpose of this study was to identify antigens ideal for a sensitive and specific serum test. We identified the specific antigens using immunoaffinity columns immobilized with IgG antibodies from periodontitis patients. Liquid chromatography-tandem mass spectrometry identified 29 antigens from the elutes. Recombinant proteins for these candidates were synthesized using the wheat germ cell-free translation system and screened by dot blot analysis with serum from the columns. Three of the 16 candidates that reacted showed strongest affinities upon dot blot analysis; they included outer membrane protein 28, cysteine proteases, lysine gingipain Kgp, and arginine gingipain RgpA. Outer membrane protein 28 was not suitable for screening P. gingivalis infection because of its high false-negative rates. Kgp and RgpA were unstable antigens since they underwent self-digestion. They were made stable by substituting the active cysteine residues in Kgp and RgpA with alanine using site-directed mutagenesis. Using the modified antigens, we demonstrated that the patient serum IgG level against RgpA was the highest among all the antigens expressed in P. gingivalis. Moreover, the N-terminus of recombinant RgpA was excellent in differentiating between diseased and non-diseased states (with sensitivity of 0.85, specificity of 0.9, and area under the curve of 0.915). Although dot blot analysis was the only experiment used, the N-terminus of RgpA is an excellent antigen to immunologically test for P. gingivalis infection, especially for estimating the risks for periodontitis-associated systemic diseases. In conclusion, we have developed a P. gingivalis antigen for screening periodontitis.

Insulin-like growth factor-1 is inversely associated with liver fibrotic markers in patients with type 2 diabetes mellitus.

AIMS/INTRODUCTION: Insulin-like growth factor-1 (IGF-1) regulates mitochondrial function, oxidative stress, inflammation, stellate cells and insulin sensitivity in the liver, and it might be associated with liver fibrosis from non-alcoholic steatohepatitis. In contrast, type 2 diabetes mellitus is closely associated with the progression from non-alcoholic fatty liver to non-alcoholic steatohepatitis and cirrhosis, so careful evaluation of liver fibrosis is required for patients with type 2 diabetes mellitus. Therefore, we examined the relationship between IGF-1 and liver fibrosis markers in type 2 diabetes patients without obvious alcoholic consumption and determined whether IGF-1 is associated with fibrosis of non-alcoholic fatty liver disease. MATERIALS AND METHODS: We selected 415 patients with type 2 diabetes without obvious alcohol consumption, who were admitted to Uwajima City Hospital between May 2013 and December 2016. We collected and analyzed clinical data to determine correlations between IGF-1 or IGF-1 standard deviation score and fibrosis-4 index or 7S domain of type IV collagen. RESULTS: Multiple linear regression analysis showed that the fibrosis-4 index was inversely correlated with IGF-1 and IGF-1 standard deviation score. Furthermore, the 7S domain of type IV collagen was also inversely correlated with IGF-1 and IGF-1 standard deviation score. CONCLUSIONS: IGF-1 was inversely correlated with liver fibrosis markers in type 2 diabetes mellitus patients without obvious alcoholic consumption. Measuring serum IGF-1 levels might help clinicians to identify type 2 diabetes mellitus patients with advanced non-alcoholic steatohepatitis.

Samarium(II)-mediated spirocyclization by intramolecular aryl radical addition onto an aromatic ring.

Samarium(II)-mediated spirocyclization by intramolecular addition of aryl radicals onto an aromatic ring was achieved by the reaction of N-(2-iodophenyl)-N-alkylbenzamides with SmI2 in the presence of HMPA, yielding spirocyclic indolin-2-one derivatives. The ether congeners afford spirocyclic benzofuran derivatives in moderate yields by aryl radical addition onto a benzene ring without having an electron-withdrawing group. The reaction with other aryl groups such as naphthalene and indole rings is also described.

[A case of gastrointestinal stromal tumor of the stomach which rapidly increased in size over the period of three years].

The patient was a 75-year-old woman. Esophagogastroduodenoscopy revealed a submucosal tumor 2 cm in size on the anterior wall of the cardiac part of the stomach. Three years later, she visited at our hospital with the chief complaints of tarry stool and dizziness. Proximal gastrectomy was performed, because endoscopically the tumor increased to 7cm in size with ulceration and it was considered to be malignant. Pathological examination was high-risk gastrointestinal stromal tumor. In this case, the submucosal tumor increased by 3.5 times. GIST is needed to be observed carefully and be treated in the appropriate time.

Successful video-assisted thoracoscopic surgery in prone position in patients with esophageal cancer and aberrant right subclavian artery: report of three cases.

BACKGROUND: An aberrant right subclavian artery (ARSA) with an associated nonrecurrent right inferior laryngeal nerve (NRILN) is a relatively rare anomaly that occurs at a frequency of 0.3 to 2.0% of the general population. NRILN has been mainly documented in the head and neck region; it has been rarely described in patients with esophageal cancer, especially those undergoing thoracoscopic surgery. Video-assisted thoracoscopic surgery for esophageal cancer (VATS-E) is becoming more widespread as a reliable minimally invasive surgical procedure associated with reduced perioperative complications. CASE PRESENTATION: Herein, we report three cases of esophageal cancer with ARSA and NRILN which underwent successful VATS-E. Case 1, a 53-year-old male who had early stage esophageal cancer was performed VATS-E. Upper gastrointestinal (GI) series showed "Bayonet sign" (T1aN0M0, pStageIA in UICC). Case 2, a 75-year-old male who had advanced esophageal cancer was performed neoadjuvant chemotherapy and following VATS-E. This case had right thoracic duct and "Bayonet sign" on upper GI series (T1bN2M0, pStage IIIA in UICC). Case3, a 72-year-old male who had advanced esophageal cancer was performed neoadjuvant chemotherapy and following VATS-E (T3N2M0, pStageIIIB in UICC). All of these three cases were performed VATS-E and discharged without any complication. CONCLUSION: VATS-E in the prone position is a feasible procedure that can reduce the risk of complications with an enlarged and clear view, and knowledge of this type of anomaly is very important for surgeons who perform esophagectomy.

A study of evolutionary multiagent models based on symbiosis.

Multiagent Systems with Symbiotic Learning and Evolution (Masbiole) has been proposed and studied, which is a new methodology of Multiagent Systems (MAS) based on symbiosis in the ecosystem. Masbiole employs a method of symbiotic learning and evolution where agents can learn or evolve according to their symbiotic relations toward others, i.e., considering the benefits/losses of both itself and an opponent. As a result, Masbiole can escape from Nash Equilibria and obtain better performances than conventional MAS where agents consider only their own benefits. This paper focuses on the evolutionary model of Masbiole, and its characteristics are examined especially with an emphasis on the behaviors of agents obtained by symbiotic evolution. In the simulations, two ideas suitable for the effective analysis of such behaviors are introduced; "Match Type Tile-world (MTT)" and "Genetic Network Programming (GNP)". MTT is a virtual model where tile-world is improved so that agents can behave considering their symbiotic relations. GNP is a newly developed evolutionary computation which has the directed graph type gene structure and enables to analyze the decision making mechanism of agents easily. Simulation results show that Masbiole can obtain various kinds of behaviors and better performances than conventional MAS in MTT by evolution.

The first samarium(II)-mediated aryl radical cyclisation onto an aromatic ring.

Intramolecular arylation of aryl radicals was mediated by SmI(2)/HMPA in the presence of i-PrOH to give spirocycles and/or reduced cine-cyclised products, while the reaction in the absence of i-PrOH gave the rearomatised fused rings.

[Antibacterial activity of new-quinolone and macrolide antibiotics against oral bacteria].

Minimum Inhibitory Concentration (MIC) of 4 new-quinolone antibacterial reagents and 4 macrolide antibiotics against periodontopathic bacteria 21 species 24 strains of standard strains including oral related bacteria and clinical isolated (1993-1999) 20 strains of Porphyromonas gingivalis, 7 strains of Actinobacillus actinomycetemcomitans were determined. Minocycline HCl was used as the comparative reagent. Macrolide showed moderate antibacterial activity against standard strains of oral related bacteria except Fusobacterium nucleatum. New-quinolone showed excellent activity against Eikenella corrodens and Actinobacillus actinomycetemcomitans. Concerning to the clinical isolated strains, Clarithromycin effected P. gingivalis (MIC90 0.1 microgram/ml) and Levofloxacin and Ciprofloxacin showed high-potency antibacterial activity against clinical isolated Actinobacillus actinomycetemcomitans (MIC90 0.013-0.025 microgram/ml).