Whole blood transcriptome profiling identifies gene expression subnetworks and a key gene characteristic of the rare type of osteomyelitis.

Chronic non-bacterial osteomyelitis (CNO) is a rare and severe inflammatory bone disorder that can occur in the jaw. It is often associated with systemic conditions including autoimmune deficiency. Medical management of patients and establishment of a correct diagnosis are difficult as the etiology of the disease remains unknown. Therefore, little is known about the disease characteristics at the gene expression level. Here, we explored aspects of CNO based on whole blood RNA sequencing (>6 Gb per sample) of 11 patients and 9 healthy controls in Japan and on a recently developed method that is applicable to small datasets, can estimate a directed gene network, and extract a subnetwork of genes underlying patient characteristics. We identified nine subnetworks, comprising 26 differentially regulated edges and 36 genes, with the gene encoding glycophorin C (GYPC) presenting the highest discrimination ability. The expression of the gene was mostly lower in patients with CNO than in the healthy controls, suggesting an abnormal status of red cells in patients with CNO. This study enhances our understanding of CNO at the transcriptome level and further provides a framework for whole blood RNA sequencing and analysis of data obtained for a better diagnosis of the disease.

Subcutaneous Migration of a Broken Dental Needle from the Mandibular Gingiva to the Neck: A Case Report.

A 33G, 12-mm needle broke and entered the soft tissue in a 60-year old man. Panoramic X-ray imaging and cone-beam computed tomography (CT), which we performed a few hours after the breakage, revealed the needle in the soft tissue of the lower right mandibular molar. We immediately made an incision in the buccal gingiva of the lower right mandibular molar under local anesthesia and attempted to remove the needle but could not locate it. Thereafter, we adopted a watch-and-wait approach, as the patient had no subjective symptoms. Nine months later, we confirmed via CT that the needle had migrated subcutaneously to the right side of the neck. Two months later, we identified its location using C-arm fluoroscopy and removed it under general anesthesia. This report is a rare case and we are the first to document the subcutaneous migration of a fractured needle.

Antimicrobial susceptibility surveillance of bacterial isolates recovered in Japan from odontogenic infections in 2013.

We report on the findings of the first antimicrobial susceptibility surveillance study in Japan of isolates recovered from odontogenic infections. Of the 38 facilities where patients representing the 4 groups of odontogenic infections were seen, 102 samples were collected from cases of periodontitis (group 1), 6 samples from pericoronitis (group 2), 84 samples from jaw inflammation (group 3) and 54 samples from phlegmon of the jaw bone area (group 4) for a total of 246 samples. The positivity rates of bacterial growth on culture were 85.3%, 100%, 84% and 88.9%, respectively, for groups 1, 2, 3 and 4. Streptococcus spp. isolation rates according to odontogenic infection group were 22% (group 1), 17.7% (group 3) and 20.7% (group 4). Anaerobic isolation rates were 66.9% (group 1), 71.8% (group 3) and 68.2% (group 4). Drug susceptibility tests were performed on 726 strains excluding 121 strains that were undergrown. The breakdown of the strains subjected to testing was 186 Streptococcus spp., 179 anaerobic gram-positive cocci, 246 Prevotella spp., 27 Porphyromonas spp., and 88 Fusobacterium spp. The isolates were tested against 30 antimicrobial agents. Sensitivities to penicillins and cephems were good except for Prevotella spp. The low sensitivities of Prevotella spp is due to ß-lactamase production. Prevotella strains resistant to macrolides, quinolones, and clindamycin were found. No strains resistant to carbapenems or penems were found among all strains tested. No anaerobic bacterial strain was resistant to metronidazole. Antimicrobial susceptibility testing performed on the S. anginosus group and anaerobic bacteria, which are the major pathogens associated with odontogenic infections, showed low MIC90 values to the penicillins which are the first-line antimicrobial agents for odontogenic infections; however, for Prevotella spp., penicillins combined with ß-lactamase inhibitor showed low MIC90 values.

Characterization of SCCmec type IV methicillin-resistant Staphylococcus aureus clones increased in Japanese hospitals.

Recently, the prevalence of staphylococcal cassette chromosome mec (SCCmec) type IV isolates, which are the major community-acquired methicillin-resistant Staphylococcus aureus (MRSA), have increased in Japanese hospitals. The aim of this study was to elucidate the detailed molecular epidemiological features of the SCCmec type IV clones in Japanese hospitals. When 2589 MRSA isolated from four hospitals in Tokyo, Japan between 2010 and 2014 were analysed, the proportion of SCCmec type IV overtook that of type II, which was the major type of hospital-acquired MRSA in 2014. Multilocus sequence typing showed that CC1 was the most predominant clone in the SCCmec type IV isolates. The clinical departments that the patients belonged to, pulsed-field gel electrophoresis analysis and antimicrobial susceptibility profiles suggested that the origin of the CC1-SCCmec type IV (CC1-IV) clone was a community setting. Our data show that the CC1-IV clone is becoming a predominant MRSA clone in Japanese hospitals.

Fatal Bleeding in Conjunction with Mandibular Medication-related Osteonecrosis of the Jaw (MRONJ).

Here, we report a case of fatal bleeding in conjunction with mandibular medicationrelated osteonecrosis of the jaw (MRONJ). A 75-year-old Japanese man was referred to our department with osteonecrosis of the jaw due to bisphosphonate (BP) for multiple bone metastases from prostate cancer. Aggressive surgical intervention was ruled out due to a poor prognosis in terms of life expectancy. Death occurred due to hemorrhagic shock resulting from massive oral bleeding caused by necrosis of the mandible. Numerous reports have suggested that jaw necrosis is induced not only by BP, but also RANKL antibody, steroids, and molecularly-targeted agents. This suggests that the number of cases of MRONJ is likely to increase among elderly patients in whom general health is already poor. The American Association of Oral and Maxillofacial Surgery recommends aggressive treatment only in cases of stage 3 disease. Therefore, such a therapeutic strategy may only be available for cases of jaw necrosis in which the general health status of the patient is otherwise good. To prevent a life-threatening outcome in cases of MRONJ, physicians, who are responsible for determining the drug strategy, should cooperate with oral surgeons in determining the best therapeutic strategy.

Characterization of methicillin-resistant Staphylococcus aureus isolated from tertiary care hospitals in Tokyo, Japan.

The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) remains problematic in both hospital and community settings. Investigations of MRSA existing in the local area are necessary to understand the detailed epidemiology of healthcare-associated MRSA (HA-MRSA). In the present study, molecular epidemiological analysis was performed on 584 MRSA isolated from four hospitals in Tokyo, Japan. In the pulsed-field gel electrophoresis (PFGE) analysis, four epidemic pulsotypes (I to IV) were found. The isolates of the epidemic pulsotype I mainly consisted of the SCCmec type II, toxic shock syndrome toxin 1 gene (tst)-negative, spa type t002, and ST764 clones. The ST764 clone, which is a novel hybrid variant of the ST5 HA-MRSA lineage with the arginine catabolic mobile element (ACME), was first found in Niigata, Japan. However, no ACME genes were detected in the isolates of the epidemic pulsotype I. In contrast, the other isolates of the epidemic pulsotypes mainly consisted of the SCCmec type II, tst-positive, spa type t002, and ST5 clones, which are the most predominant clones of HA-MRSA in Japan. Resistance rates of non-ß-lactams for the isolates of the epidemic pulsotype I were higher than those of the other epidemic pulsotypes. Our data showed that the novel ACME-negative ST764 clones are being distributed throughout multiple hospitals in Tokyo. The ST764 clones in Tokyo have the potential to acquire ACME in the future, because the ACME-positive ST764 clones have already been found in both hospital and community settings in other areas of Japan.

Postoperative follow-up strategy in patients with oral squamous cell carcinoma.

PURPOSE: The duration of follow-up after treatment of oral squamous cell carcinoma and the frequency of routine visits are based on common usage rather than evidence-based practice. The purpose of this study was to determine the appropriate postoperative routine follow-up program in patients with oral squamous cell carcinoma. PATIENTS AND METHODS: Three hundred four cases treated curatively mainly by surgery at Tokai University Hospital from 1994 to 2004 were analyzed. A secondary event was defined as a local recurrence, a regional recurrence, a distant metastasis, or a second primary cancer. To evaluate the follow-up program, data on the first tumor recurrence or first second primary tumor in the head and neck region or elsewhere in the body were used. Overall survival rate, disease-specific survival rate, relapse-free rate, and cumulative risk of developing a second primary cancer were estimated by the Kaplan-Meier product limit method. RESULT: All relapse cases were detected within 3 years postoperatively, of which 86.3% were detected within 1 year. Most relapses were in the neck, and regional recurrences had a dismal salvage rate. Second primary cancers were constantly detected 1 to 10 years postoperatively. CONCLUSION: Follow-up should be performed more frequently in the first year, with 2 weekly follow-ups with monthly ultrasound examinations, and should be continued after 3 years to exclude the development of second primary cancers.

Identification of oral bacteria by 16S rRNA gene analysis in elderly persons requiring nursing care.

After incubation of saliva from 58 semi-bedridden elderly persons, the cultures were identified based on the 16S rRNA gene base sequence to compare the identification by the conventional culture method. As a result, the 16S rRNA gene base sequence of 198 strains identified by the culture method showed 98.5% or more homology in some of the Human Oral Microbiome database, and the identification of bacterial species and genus was possible. When an organism identified by the 16S rRNA gene sequencing method was compared with that by the culture method, the concordance rates were 54.5% at the genus level and 35.9% at the species level. Streptococcus mitis strains most frequently isolated from saliva that were identified by the culture method were identified as the same species by the 16S rRNA gene sequencing method (32/35), and all the 11 Streptococcus salivarius strains identified by the culture method were identified as the same species by the 16S rRNA gene sequencing method. All the strains identified as Streptococcus anginosus group by the culture method and 8 of the 9 strains identified as Prevotella species by the culture method were identified as the same group and genus by the 16S rRNA gene sequencing method. When an oral microbial flora test with saliva samples from elderly persons is performed, the 16S rRNA gene sequence identification enables us to identify major indigenous bacteria and pathogenic bacteria and is considered useful as a means of supplementing the conventional culture method.

Ameloblastic carcinoma, secondary type: a case report.

Malignant variants of ameloblastoma include metastasizing ameloblastoma, which microscopically appears benign but has metastasized and ameloblastic carcinoma that exhibits malignant histopathologic features. Ameloblastic carcinoma is classified into 2 types: a primary odontogenic malignancy and a secondary type resulting from malignant transformation of ameloblastoma. Most secondary ameloblastic carcinomas result from malignant transformation of a primary lesion after repeated postsurgical recurrences. Therefore it is rare to find an untreated secondary type presenting with histologic features of malignant transformation from an earlier benign lesion. We experienced a rare case of ameloblastic carcinoma, secondary type which might arise in an untreated ameloblastoma. The mechanism by which a preexisting benign ameloblastoma goes through a malignant transformation is also described.

Analysis of risk factors for surgical-site infections in 276 oral cancer surgeries with microvascular free-flap reconstructions at a single university hospital.

The purpose of this study was to elucidate the risk factors for surgical-site infection (SSI) in oral cancer surgery with microvascular free-flap reconstructions and to propose appropriate SSI prevention. There were 276 patients who underwent oral cancer surgery with microvascular free-flap reconstructions at the Department of Oral and Maxillo-facial Surgery of Tokai University Hospital. The following variables were assessed as risk factors for SSIs: preoperative variables, including age, sex, body mass index, American Society of Anesthesiologist's (ASA) score, debilitating comorbidities, smoking, alcohol consumption, and Union Internationale Contre le Cancer Tumor Node Metastasis (UICC-TNM) classification; and operative variables, including duration of surgery, amount of blood loss, quantity of blood transfusion, tracheostomy, area of neck dissection, and previous chemotherapy. Statistical analysis was conducted to determine whether these factors constitute risks for SSI. Total overall SSI rate was 40.6% (112/276). When the occurrence of SSI was compared with the variables, ASA score (P=0.036), T stage (P=0.013), duration of surgery (P<0.001), blood loss (P=0.001), blood transfusion (P=0.01), and area of neck dissection (P=0.009) showed statistical significance. Analysis of these variables with a logistic regression model yielded ASA score and duration of surgery as significant factors. There was a tendency for blood loss and duration of surgery to increase in patients with a high T stage. A high T stage not only broadens the resection area and increases surgical invasiveness, it also increases susceptibility to dead space after microvascular reconstruction for oral cancer. Particular care in treating the wound should be taken in surgical patients with high T-stage scores. The occurrence of SSI is of particular concern in oral cancer surgery in patients with high ASA scores.

A case of brain abscess extended from deep fascial space infection.

A case of brain abscess in the temporal lobe caused by direct intracranial extension of deep neck abscess is described. The abscess also spread to the orbital cavity through infraorbital fissure. The possible etiology of this case might be dental surgery. The diagnostic imaging clearly showed the routes of intracranial and -orbital extension of parapharyngeal and masticator space abscesses. From the abscess specimens, oral streptococci, anaerobic streptococci, and anaerobic gram-negative bacilli were isolated. Antimicrobial susceptibility testing of isolates showed that some Prevotella and Fusobacterium strains had decreased susceptibility to penicillin, and these bacteria produced beta-lactamase. The bacteria from the deep neck abscess were consistent with those detected from the brain abscess. Proper diagnosis, aggressive surgical intervention, and antibiotics chemotherapy saved the patient from this life-threatening condition.

Antibiotic prevention of infective endocarditis due to oral procedures: myth, magic, or science?

Infective endocarditis (IE) can be induced by bacteremia attributable to dental procedures. To prevent this disease, prophylactic administration of antimicrobials prior to dental procedures has been recommended in several countries. However, no prospective study has proved its efficacy in a clinical setting. Recent recommendations from the American Heart Association (AHA) strongly suggested that dental work is not an important cause of IE; therefore, prophylactic use of antibiotics is of no use in most cases. Prevention of IE may be essential but its pathology and epidemiology remain unclear in various aspects. This article reviews the theoretical background of IE prophylaxis, and discusses how we should proceed when patients with a known cardiac disorder visit the dental clinic. The discussion includes antibiotics usage, daily maintenance procedures, and a possible new strategy with the use of antibacterial substances.

Necrotizing Fasciitis of the Neck due to an Odontogenic Infection: A Case Report.

Deep fascial space infections of the neck are most frequently odontogenic in origin. We describe a case of odontogenic infection of the mandible which extended to the lateral pharyngeal space and resulted in a severe life-threatening necrotizing fasciitis of the neck. A 69-year-old nondiabetic male complained of dysphagia and a severe toothache of the lower left molar and was transported to the emergency ward. A CT scan revealed swelling of the peritonsillar, lateral pharyngeal and masticator space with narrowing of the airway of the middle pharynx. The patient underwent a tracheotomy with surgical drainage. The strap muscles, including the fascia, of the neck were necrotic. He was treated with a combination of ampicillin and clindamycin-2-P. On the second postoperative day, the patient's platelet count fell to 20,000/mm3. The patient was transfused with platelet concentrate, and given gamma globulin and gabexate mesilate, and his predisseminated intravascular coagulation (DIC) status improved. However, on the eight post operative day, progressive tissue necrosis of the face and neck was observed. Panipenem betamipron was started and continued for 20 days. A second extensive surgical debridement of the neck and face was carried out, and the patient ultimately recovered. Prevotella buccae, Streptococcus intermedius, Lactobacillus fermentum, L. casei, L. catenaforme, L. acidophilus, and Bifidobacterium sp. were isolated from either the peritonsillar, submandibular, lateral pharyngeal or carotid space abscesses. We emphasize the importance of proper diagnosis, early surgical intervention and systemic antimicrobial chemotherapy to control this aggressive infectious disease.