Surveillance of multi-drug resistance phenotypes in Staphylococcus aureus in Japan and correlation with whole-genome sequence findings.

BACKGROUND: Antimicrobial resistance in Staphylococcus aureus imposes a high disease burden. Both phenotypic and genotypic monitoring are key to understanding and containing emerging resistant strains. AIM: Phenotypic monitoring of emerging resistance in S. aureus and correlation of priority strain phenotypes with whole-genome sequencing (WGS) findings. METHODS: Antimicrobial susceptibility test results of >40,000 isolates from 213 participating hospitals from 2011 to 2019 were exported from the national Japan Nosocomial Infections Surveillance (JANIS) database. Longitudinal and geographic distribution and prevalence of distinct multi-drug resistance phenotypes ('resistance profiles') of S. aureus were examined among hospitals and prefectures. We further conducted a genome sequence analysis of strains with specific resistance profiles of concern. FINDINGS: The overall prevalence of meticillin-resistant S. aureus (MRSA) decreased from 40.3% to 35.1% from 2011 to 2019. However, among dozens of S. aureus resistance profiles, only one profile of a type of MRSA, exhibited a statistically significant increase in inpatient frequency, exceeding 10% during the nine years. This MRSA profile showed resistance to oxacillin, erythromycin and levofloxacin. Analysis of WGS results of S. aureus isolates with this phenotype revealed that most belonged to clonal complex 8, and all carried SCCmec IV, typical of community-acquired MRSA. CONCLUSION: Tracking distinct resistance profiles deepened our understanding of the overall decrease in MRSA and led to recognition of the emergence of a new resistance phenotype. This study provides a model for future epidemiological research on antimicrobial resistance correlating multi-drug resistance phenotypes with selective genome sequencing, which can be applied to other bacterial species.

Comparison of mouse and human ankles and establishment of mouse ankle osteoarthritis models by surgically-induced instability.

OBJECTIVE: Prevalence of ankle osteoarthritis (OA) is lower than that of knee OA, however, the molecular mechanisms underlying the difference remain unrevealed. In the present study, we developed mouse ankle OA models for use as tools to investigate pathophysiology of ankle OA and molecular characteristics of ankle cartilage. DESIGN: We anatomically and histologically examined ankle and knee joints of C57BL/6 mice, and compared them with human samples. We examined joints of 8-week-old and 25-month-old mice. For experimental models, we developed three different ankle OA models: a medial model, a lateral model, and a bilateral model, by resection of respective structures. OA severity was evaluated 8 weeks after the surgery by safranin O staining, and cartilage degradation in the medial model was sequentially examined. RESULTS: Anatomical and histological features of human and mouse ankle joints were comparable. Additionally, the mouse ankle joint was more resistant to cartilage degeneration with aging than the mouse knee joint. In the medial model, the tibiotalar joint was markedly affected while the subtalar joint was less degenerated. In the lateral model, the subtalar joint was mainly affected while the tibiotalar joint was less altered. In the bilateral model, both joints were markedly degenerated. In the time course of the medial model, TdT-mediated dUTP nick end labeling (TUNEL) staining and Adamts5 expression were enhanced at early and middle stages, while Mmp13 expression was gradually increased during the OA development. CONCLUSION: Since human and mouse ankles are comparable, the present models will contribute to ankle OA pathophysiology and general cartilage research in future.

Effect of periodontal surgery on oral health-related quality of life in patients who have completed initial periodontal therapy.

BACKGROUND AND OBJECTIVE: Patient-centered assessments are particularly important in periodontal treatment in which their concerns may differ from the traditional clinical endpoints. However, information is limited regarding the influence of periodontal surgery on patients' quality of life (QoL). The aim of the present study was to investigate the impact of surgical periodontal therapy on the oral health-related QoL of patients who have received initial periodontal therapy. METHODS: A three-center prospective clinical study design was used, with the study participants comprising patients with moderate to severe periodontitis. Following initial periodontal therapy, the participants received either surgical or non-surgical periodontal treatment. The Oral Health-related Quality of Life Model for Dental Hygiene (OHRQL instrument), was used to assess participants' oral health-related QoL at each periodontal assessment interval: baseline (phase I), after initial therapy (phase II) and after surgery or during supportive periodontal therapy (phase III). RESULTS: Seventy-six patients (26 non-surgery, 50 surgery) completed the third phase of OHRQL assessment and were subjected to data analysis. From phase II to III, an improvement was achieved in all clinical parameters (p < 0.05-0.001) in the surgery group, whereas no such improvement was observed in the non-surgery group. In both groups, a significant difference in total OHRQL score was noted between phases I and III (p < 0.001 for surgery and p < 0.05 for non-surgery). The OHRQL domain scores for pain and eating/chewing function showed a significant improvement between these time points. However, no further significant improvement in OHRQL scores was achieved from phase II to III. CONCLUSION: A significant improvement in oral health-related QoL was noted between phases I and III in the surgery and non-surgery groups. Such improvement was less pronounced in the non-surgery vs. the surgery group. From phase II to III, neither surgery nor non-surgical treatment yielded significant improvement in oral health-related QoL.

Repair of segmental ulna defects using a ß-TCP implant in combination with a heparan sulfate glycosaminoglycan variant.

Given the wide spread clinical use of ceramic-based bone void fillers, we sought to determine the efficacy of an FDA-approved ß-tricalcium phosphate bone graft substitute (JAX™) in combination with a carboxymethyl cellulose (CMC) handling agent that included a particular heparan glycosaminoglycan (GAG) variant, herein referred to as HS3. Having recently demonstrated efficacy of a combination collagen/HS3 device, we further aimed to determine the support that HS3 could offer a handling agent used to administer a more tissue-relevant bone void filler. This study evaluated the JAX™-HS3 combination device in 1.5 cm critical-sized defects in the ulna bones of 27 male New Zealand White rabbits. Treatment groups consisted of JAX™ applied with CMC alone, or JAX™ with CMC containing either 30 µg or 100 µg of the HS3 GAG. Data based on radiographic, µCT, mechanical, and histological analyses at 4 and 8 weeks post-surgery, clearly demonstrate enhanced new bone formation in the JAX™-HS3 combination treated defects compared to treatment with JAX™ alone. The efficacy of such a combination advocates for inclusion of HS3 in handling agents used in the preparation of various bone void fillers being used in orthopaedic surgery. STATEMENT OF SIGNIFICANCE: Synthetic bone grafts and demineralized bone matrices are gaining prominence as alternatives to autologous and allogeneic bone grafts and are frequently administered in granular form, necessitating their combination with a handling agent. Typical handling agents include glycerol, gelatin, cellulose, hyaluronic acid and lecithin, formulated as hydrogels, which can be further enhanced by the addition of heparan sulfate (HS) glycosaminoglycans that augment the osteostimulatory properties of the graft. Here we assessed the efficacy of ß-TCP granules combined with a hydrogel consisting of carboxymethyl cellulose and the HS variant (HS3) previously shown to enhance osteogenic healing. The data advocates for HS3 to be included during the formulation of hydrogel-based carriers that support the various bone void fillers being used in orthopaedic surgery.

Prenatal development of the eye tunics in the dromedary camel (Camelus dromedarius).

Studies of ocular development in the dromedary camel (Camelus dromedarius) have not been reported previously. The aim of the present investigation was therefore to document the major landmarks and the time course in the prenatal development of the eye tunics in dromedary camel and its accommodation with the surrounding hard environment of the desert. Serial histological sections of dromedary camel embryos and foetuses were used. Age estimation was made on the basis of gestational size, crown vertebral-rump length (CVRL), which ranged 1.2-110 cm. The eye of the dromedary camel developed in a similar manner to that of the human and domestic animals eyes; the principal differences were in the time of occurrence of certain developmental events, pigmented peripheral cornea near the limbus, a remarkably thickened Descemet's membrane and pigmentation in the corneo-scleral junction, which represent an adaptive modification in relation to a severe environment.

[Neonatal molding for minor deformities of auricular cartilage: a simple method]. / Modelage néonatal des déformations mineures du cartilage auriculaire : une méthode simple.

Non-surgical correction of minor ear deformities by external splinting during neonatal age is a well-known, effective technique, but not frequently used in France. We would like to popularize an established, simple method that uses cheap, available means (a wire, adhesive strips and a silicone probe). It can be performed by parents, paediatricians and nurses. Spreading this method would allow early onset of treatment and better clinical results. On the long run, it would have a certain economic aftermath on national health insurance by reducing the number of surgical procedures for deformed ears.

[Cleft lip and palate management by Pr Hosaka's team at the Showa University, Tokyo (Japan)]. / Prise en charge des fentes labiopalatines par l'équipe du Pr Hosaka à l'université de Showa, Tokyo (Japon).

We describe the particularities of cleft lip and palate treatment in the department of plastic surgery managed by Pr Hosaka at the Showa University in Tokyo. Their surgical technic inherited from Pr Onizuka, their multidisciplinary approach, and their experience with over 300 cases a year were not reported in a non-Japanese journal. Therefore, we found interesting to describe their whole management.

Expressions of apoptosis-regulating factors in bovine retained placenta.

The aim of the present study was to evaluate the relationship between the retention of fetal membranes (RFM) and apoptosis of the cells in fetal membranes. The present study investigated mRNA and protein expressions of apoptosis-regulating factors: FAS, cellular FLICE-like inhibiting protein (cFLIP), BAX, BCL2, caspase-8 (CASP8), and CASP3 in fetal membranes. Placentomes were manually collected from the uterus immediately after parturition and classified into two groups (RFM; n = 8 and non-RFM; n = 8) according to whether placental membranes were expelled or not within 12 h after delivery. FAS mRNA expression in maternal placental tissue was less in RFM cows than in non-RFM cows (P < 0.05). cFLIP mRNA expression in maternal and fetal placental tissue was greater in RFM cows than in non-RFM cows (P < 0.05). CASP3 mRNA expression in maternal placental tissue was greater in RFM cows than in non-RFM cows (P < 0.05). However, the protein expressions of FAS, cFLIP and cleaved CASP3 were not significantly different between the two groups. mRNA and protein expressions of BAX, BCL2 and CASP8 were also not significantly different between the two groups. In the immunohistochemical study, single-stranded DNA, which appears specifically in the apoptotic cells, was mainly found in the maternal placenta of non-RFM cows. Together these results suggest that RFM occurs at least in part due to a dysfunctional apoptotic process caused by the inhibition of FAS expression in the maternal placenta, and the increase of cFLIP expression in the maternal and fetal placenta.

[Pure red cell aplasia after resection for thymoma with myasthenia gravis].

A 73 year-old woman was diagnosed as thymoma with myasthenia gravis (MG) [ocular type] 18 years ago, but she rejected surgical treatment. The remission of myasthenia gravis has been obtained by treatment of medication. This time, to avoid myasthenic crisis at the time of orthopedic surgery, she underwent surgical treatment for thymoma: extended-thymectomy, resection of the left brachiocephalic vein and reconstraction using ringed polytetrafluoroethylene (ePTFE) graft. Pathologic diagnosis was Masaoka stage III thymoma and World Health Organization (WHO) type B2 + B3. After orthopedic surgery, irradiation was performed for mediastinum. During this period from the resection of thymoma to irradiation, she developed gradually progressive anemia, and as a result of bone marrow examination, she was diagnosed as pure red cell aplasia (PRCA). PRCA has improved with immunosuppressive treatment. One year have passed with no recurrence of thymoma and PRCA.

[Induction chemoradiation followed by resection through anterior approach for superior sulcus tumor].

Two cases of induction chemoradiation followed by surgical resection were reported. A 53-year-old man and a 68-year-old man who had been suffering form alleviate pain in their left shoulder and arms were referred to our hospital. Physical examination revealed Horner's syndrome on the left side in both patients. A transcutaneous needle biopsy confirmed non-small-cell lung cancer. Under the diagnosis of superior sulcus tumor in stage IIIB (T4N0M0), induction chemotherapy and radiation were given. After tumor reduction, they underwent resection through cervical anterior approach because subclavian vessel invasion was suspected. The clavicle was divided for the resection and reconstruction of subclavian artery in case 2. For the treatment of anterior superior sulcus tumors, anterior approach provides a safe and effective exposure.

[Single-stage operation for synchronous bilateral multiple lung cancer through median sternotomy].

An asymptomatic 65-year-old woman was incidentally found to have abnormal shadows on a chest X-ray during a medical examination. A chest computed tomography (CT) scan showed a pulmonary nodule in both right and left lung. Those were diagnosed as synchronous cStage IA bilateral lung cancer, and right upper lobectomy and segmentectomy of the left lung with lymphoadenectomy were sequentially performed through median sternotomy. The patient showed a favorable course after surgery, and was discharged on postoperative day 12. The pathological diagnosis was synchronous lung cancer and both were adenocarcinoma. The pathological stage was IA on the right side and IB on the left. A single-stage operation through median sternotomy was a useful surgical procedure for treating this case of synchronous bilateral lung cancer.

[Tracheal resection and reconstruction for tracheal stenosis].

Five patients underwent surgery for tracheal stenosis. The cause of stenosis was congenital tracheal stenosis in 1 case, post-intubation tracheal stenosis in 1 case, and tracheal stenosis due to thyroid cancer invasion in 3 cases. All 5 patients required circumferential tracheal resection and end-to-end anastomosis using 4-0 or 5-0 absorbable sutures. The number of tracheal rings removed ranged from 3 to 6. There was no anastomotic complication. Technical points of this procedure were summarized as follows : 1) the circumferential dissection of the trachea should be made only at the level of the lesion that is to be excised, 2) preserve at least one side of recurrent nerve, 3) the traction sutures facilitate tensionless knot of the sutures, 4) prevention of excessive extension of the neck in the immediate postoperative period.

[Primary spontaneous pneumomediastinum].

We report 5 cases of spontaneous pneumomediastinum. They were 4 men and 1 female with a mean age of 17 (14-25). Four patients developed sport-related pneumomediastinum and 1 patient had a karaoke-related condition. Primary spontaneous pneumomediasinum is a rare condition. In addition, there is no previous report describing karaoke-related spontaneous pneumomediastinum. Each of the patients experienced chest pain and/or neck pain before consulting our hospital. Chest roentgenogram and chest computed tomography showed pneumomediastinum without esophageal or tracheal injury. Four patients did not require hospitalization, but 1 patient was necessary to hospitalize for 7 days because of severe chest and neck pain. None of these 5 patients has had any recurrence for more than 1 year. Differentiating this entity from other diseases involving anterior chest pain is important.

[Thymoma transformed to thymic carcinoma with brain and bone metastases 6 years after recurrence].

We report a man who developed brain and bone metastases 6 years after resection of recurrent thymoma. The patient underwent surgery for B2-thymoma [World Health Organization (WHO) classification] without microscopic capsular invasion at 50-year-old. The next year, he underwent the second surgery for recurrent B2-thymoma as pleural dissemination. Seven months after the second surgery, he developed recurrence of pleural dissemination. The patient refused any further aggressive treatment, including surgery, chemotherapy, and radiotherapy. The pleural disease did not increase over 6 years, then suddenly enlarged. Thereafter, the patient developed left hemiparesis due to brain metastases, followed by bone metastases. Immunochemical studies of the metastatic tumors demonstrated that these lesions seemed to be poorly differentiated thymic carcinoma (small cell carcinoma) on WHO classification. We concluded that the thymoma transformed to thymic carcinoma with brain and bone metastases during 6 years.

[Sarcomatoid pleural mesothelioma presenting as posterior mediastinal tumor with dysphagia].

Case 1: A 46-year-old man with dysphagia, chest pain and cough admitted to our department. Radiological studies demonstrated a solid mass with a maximal diameter of 5cm at the posterior mediastinum. The tumor was resected, then postoperative radiotherapy (60Gy) and chemotherapy were performed. Results of histological and immunohistochemical study showed that the tumor consisted of sarcomatoid mesothelioma. The patient died of recurrence with bone metastasis 6 months after surgery. Case 2: A 76-year-old man with dysphagia, chest pain and cough admitted to our department Radiological studies demonstrated a solid mass with a maximal diameter of 12cm in the posterior mediastinum. accompanied by abundant effusion in the bilateral pleural cavities. The patient underwent open biopsy and histological and immunohistochemical study showed that the tumor consisted of sarcomatoid mesothelioma. The patient died of multiple organ failure on the 1st postoperative day. We report extremely rare cases of sarcomatoid mesothelioma that appeared to be posterior mediastinal tumor before surgery, and discuss the difficulty of diagnosing sarcomatoid mesothelioma with atypical clinical manifestations.

Intranuclear paracrystals observed in striated muscle specific LIM protein-deficient mouse cardiomyocytes.

A paracrystalline structure was observed within left ventricular cardiomyocyte nuclei of MLP(-/-) mice. The paracrystal possessed cross lines, approximately 8.0 micro m long and 0.3 micro m wide, with a slender spindle shape and a periodicity of 13 nm. Paracrystals were best observed along the longitudinal orientation of myofibrils and were detected in less than 10% of the nuclei observed. One dimension of the protein unit forming the paracrystal was 8.5 nm long. The electron density of the paracrystal appeared to be slightly higher than that of heterochromatin, suggesting that RNA-associated proteins are constituents of the paracrystal. This is the first report of intranuclear paracrystals in cardiomyocytes, which appear to be unique to MLP(-/-) mice.

[Primary lung cancer incidentally diagnosed in lung biopsy for diffuse pulmonary disease].

UNLABELLED: We here presented 2 cases of interstitial pneumonia with lung adenocarcinoma incidentally diagnosed by partially resected lung for diffuse pulmonary disease. CASE 1: A 78-year-old female was admitted to the hospital complaining of productive cough and general fatigue. The chest computed tomography (CT) revealed diffuse honey comb pattern in bilateral lung field especially in the right lower lung. Video-assisted thoracoscopic lung biopsy was performed and was diagnosed as diffuse spreading well differentiated adenocarcinoma. CASE 2: A 59-year-old male was admitted to the hospital complaining of dyspnea and general fatigue. The chest X-ray revealed right pneumothorax and chest CT revealed diffuse honey comb pattern and bullae in bilateral lung field and fibrous tumor-like lesion in the right middle lung. Video-assisted thoracoscopic lung biopsy was performed and was diagnosed as pulmonary fibrosis with papillary adenocarcinoma. CONCLUSION: It is important to examine carefully the specimen obtained from thoracoscopic lung biopsy even if interstitial pneumonia is strongly suspected.

Mechanism of cell death in inflamed superficial digital flexor tendon in the horse.

The aim of the present study was to clarify the presence and determine the role of apoptosis in the degenerative process of the superficial digital flexor tendon (SDFT) in the horse. Samples were obtained from normal and inflamed SDFTs of horses. To detect apoptosis and to identify apoptotic cells, the samples were subjected to immunohistochemical labelling and Western blot analysis. Although a large number of cells in degenerate areas showed positive reactions with caspase-3 and single stranded DNA antibodies, cells in normal tendon samples showed very weak reactions. Excessive apoptosis was confirmed by the results of Western blot analysis, which showed a significant increase in activated caspase-3 protein in the inflamed SDFTs, suggesting that apoptosis occurred in the tendinocytes via a caspase-3-dependent pathway. This is the first report of excessive apoptosis in inflamed SDFT of the horse. The results indicate that apoptosis may play an important role in the process of degeneration of the tendon as well as other tissues.

Effect of trapidil on effector functions of monocytes related to atherosclerotic plaque.

The infiltration and activation of inflammatory cells play an important role in the formation and stability of coronary atherosclerotic plaque in patients with acute coronary syndrome. In this study, we evaluated the effect of trapidil, an anti-platelet agent, on atheroma-related functions of human T cells and monocytes. Trapidil and anti-CD154 (CD40 ligand) antibody inhibited the increase of procoagulant activity in the mixed lymphocyte reaction; trapidil also suppressed the induction of tissue factor, monocyte chemoattractant protein-1 (MCP-1) and matrix metalloproteinase-9 in the mixed lymphocyte reaction. Trapidil did not alter CD154 expression on isolated T cells, but it diminished CD40 expression on isolated monocytes and human monocytic leukemia THP-1 cells stimulated with interferon-gamma. Moreover, trapidil reduced MCP-1 production of isolated monocytes and THP-1 cells stimulated with interferon-gamma plus CD154-transfected cells. This effect was not seen with other tested anti-platelet agents and coronary vasodilators. In conclusion, trapidil directly acts on monocytes/macrophages to lower their susceptibility to CD154 on T cells.

Inappropriate discharges by fourth generation implantable cardioverter defibrillators in patients with ventricular arrhythmias.

The study prospectively investigated the incidence, cause and efficient management of inappropriate discharge by the fourth generation implantable cardioverter-defibrillator (ICD) system in 45 patients (mean age, 57+/-16 years). During the follow-up period of 27+/-17 months, 18 patients (40%) experienced one or more inappropriate therapies: sinus and supraventricular tachycardia (15 patients) and T wave oversensing (3 patients). In the 15 patients, re-programming of the tachycardia detection interval and/or additional treatment with beta-blocking agents were effective. In the 3 patients with T wave oversensing, the arrythmia was associated with an increase in T wave amplitude, change in T wave morphology and decreased R wave amplitude, and re-programming of the sensitivity of the local electrogram or changing the number of intervals to detect ventricular tachycardia decreased the number of inappropriate discharges in all 3 patients. In conclusion, inappropriate therapies are common problems in patients treated with the fourth generation ICD system, but most of them can be resolved using the dual-chamber ICD system. However, in patients with T-wave oversensing, it is difficult to avoid inappropriate discharge completely, even if the dual-chamber ICD system is implanted.