Sakiko Soutome

Evaluation of the Treatment Strategies for Medication-Related Osteonecrosis of the Jaws (MRONJ) and the Factors Affecting Treatment Outcome: A Multicenter Retrospective Study with Propensity Score Matching Analysis†

Medication‐related osteonecrosis of the jaw (MRONJ) is an adverse event that may inhibit the treatment of primary disease and remarkably influence the patients quality of life. The treatment methods for MRONJ, nonsurgical and surgical, are controversial, with no agreement as to which method provides the best outcome and should therefore be recommended. This multicenter retrospective study aimed to investigate the treatment methods and outcome in a large number of patients with MRONJ in Japan, utilizing propensity score matching analysis. A total of 361 patients with MRONJ, at eight hospitals, were registered in this study retrospectively. Various demographic and treatment‐related variables were examined and analyzed to determine their correlation with the treatment outcome. After propensity score matching for treatment methods (nonsurgical versus surgical treatment), 176 patients were analyzed by logistic regression. It was shown that those with low‐dose administration of an antiresorptive agent and surgical treatment had better outcomes. Furthermore, in 159 patients who underwent surgical treatment, those who underwent extensive surgery experienced significantly better treatment outcomes than those who underwent conservative surgery. This is the first study to compare treatment methods for MRONJ using propensity score matching analysis. The results indicated that extensive surgical treatment should be performed as first‐choice therapy for patients with MRONJ.

Inhibition of fibronectin binding of some bacterial cells by subtle pH increase within the physiological range.

The fibronectin (Fn)-binding ability of microorganisms is considered to be involved in their pathogenicities. Granulicatella adiacens, a member of the oral flora and a causative agent of culture-negative infective endocarditis, showed nearly maximum binding to immobilized Fn at pH 7.2 but greatly reduced binding at a slightly higher pH 7.4 and almost no binding at pH 7.6 in the presence of physiological concentration of NaCl (0.15 M). A similar pH-sensitive Fn-binding property was noted with Escherichia coli and Abiotrophia defectiva, but not with Streptococcus pyogenes nor Staphylococcus aureus. In contrast, bindings to laminin and fibrinogen observed for some of these strains were unaffected by the same pH changes. This fastidious pH-dependency of Fn-binding abilities of some bacteria warns that the pH condition must be seriously considered in the in vitro assay of bacterial adherence to fibronectin.

Effect of perioperative oral care on prevention of postoperative pneumonia associated with esophageal cancer surgery: A multicenter case–control study with propensity score matching analysis

Abstract The aim of this study was to investigate the effectiveness of oral care in prevention of postoperative pneumonia associated with esophageal cancer surgery. Postoperative pneumonia is a severe adverse event associated with esophageal cancer surgery. It is thought to be caused by aspiration of oropharyngeal fluid containing pathogens. However, the relationship between oral health status and postoperative pneumonia has not been well investigated. This study included 539 patients with esophageal cancer undergoing surgery at 1 of 7 university hospitals. While 306 patients received perioperative oral care, 233 did not. Various clinical factors as well as occurrence of postoperative pneumonia were retrospectively evaluated. Propensity-score matching was performed to minimize selection biases associated with comparison of retrospective data between the oral care and control groups. Factors related to postoperative pneumonia were analyzed by logistic regression analysis. Of the original 539 patients, 103 (19.1%) experienced postoperative pneumonia. The results of multivariate analysis of the 420 propensity score-matched patients revealed longer operation time, postoperative dysphagia, and lack of oral care intervention to be significantly correlated with postoperative pneumonia. The present findings demonstrate that perioperative oral care can reduce the risk of postoperative pneumonia in patients undergoing esophageal cancer surgery.

Combined use of self-efficacy scale for oral health behaviour and oral health questionnaire: A pilot study

Objective: To examine whether the combined use of a task-specific self-efficacy scale for oral health behaviour (SEOH) and an oral health questionnaire (OHQ) would be useful for evaluating subjects’ behaviours and cognitions. Design: Questionnaires. Methods: One hundred and eighty-five students completed the SEOH and OHQ. The 30-item OHQ uses a nominal scale, and the 25-item SEOH includes four subscales with items rated on a five-point Likert scale. The SEOH score of each student was evaluated on the basis of the sum of all scores. The relationship between SEOH scores, including scores on all subscales, and observed values on the OHQ was examined using chi-square tests and logistic regression analysis. Results: Female subjects exhibited higher average scores than male subjects on both the SEOH and self-efficacy scale. Logistic regression analysis revealed eight significant interactions between scores on the SEOH, including its subscales, and OHQ items for male and 10 significant interactions for female. Conclusion: Combining the SEOH and the OHQ is useful as a psychological criterion for the clinical assessment and prediction of motivation and skills with respect to oral health behaviour.

Gene cloning and characterization of Streptococcus intermedius fimbriae involved in saliva-mediated aggregation

Streptococcus intermedius, an oral commensal and a cause of systemic pyogenic disease, expresses fimbriae. To identify the gene(s) encoding these fimbriae, we used a serum raised against purified fimbriae to screen libaries of recombinant lambda phages. The cloned gene cluster encoding S. intermedius fimbriae, (saliva-mediated aggregation and adherence-associated fimbriae), contained 4 ORFs, i.e. a putative ribonulease (Saf1), a putative adhesin (Saf2), the main pilus subunit (Saf3) and a sortase C (SrtC). Escherichia coli strains harboring recombinant phages and plasmids carrying the saf3 gene produced a 55kDa protein recognized by the antifimbriae serum. Saf3 contains an N-terminal signal sequence and a C-terminal cell-wall-anchoring motif LPXTG. Among strains of the Streptococcus anginosus group, only serotype g and untypable strains were found to contain the saf3 gene, to possess the fimbrial antigen and to exhibit saliva-mediated aggregation. Knockout mutants made by insertion of an erythromycin resistance gene into saf3 did not produce fimbrial structures or fimbrial antigens and did not participate in saliva-mediated aggregation. The adherent activity of mutants toward plastic wells coated with salivary agglutinin was about 65% that of the parental strain, and the reaction depended on calcium. There was no significant difference in adherence to hydroxyapatite beads pretreated with salivary agglutinin between the parental and mutant strains. These results demonstrated that Saf3 is associated with aggregation, and suggested that other molecule(s) are associated with adherence of S. intermedius.

Screening of Peptides that Inhibit Bacterial Binding to Fibronectin using Combinatorial Peptide Libraries

Infective endocarditis is often caused by passage of oral endogenous bacteria into the blood stream. Such bacteremia occurs after tooth extraction, and occasionally even after brushing of the teeth. Abnormal or damaged heart valves, including artificial valves, show high risk of infection. Antibiotics are widely used to prevent this infection, however, frequent use of these have resulted in the generation of resistant mutants, which generate serious social problems. Thus, the development of more effective and safer drugs for the prevention of such infections is very desirable. The adhesion of bacteria to fibronectin, one of the major extracellular matrix (ECM) protein exposed on the wound endocardia, is considered critical for the infection. We have previously found a novel mode of interaction between endocarditis-causing bacteria and human fibronectin. The present study focuses on the discovery of candidate compounds that inhibit the association between microorganisms and fibronectin. Positional scanning libraries (PSL) with N-terminal biotinylated 6-mer peptides have been constructed and screened for binding to a monoclonal antibody for fibronectin that inhibits the bacterial fibronectin-binding. The consensus sequences derived from these experiments are expected to be structural mimetics of the local structure of fibronectin involved in the bacterial adhesion. Since individual synthetic 6-mer peptides did not show the desired action, discontinuous epitopes can be envisaged and therefore a 9-mer-PSL was constructed to reveal conformational epitopes. In the second library, several 9-mer peptides based on the screening were synthesized and gave improved results.

Factors affecting development of medication-related osteonecrosis of the jaw in cancer patients receiving high-dose bisphosphonate or denosumab therapy: Is tooth extraction a risk factor?

Methods for preventing medication-related osteonecrosis of the jaw (MRONJ) in cancer patients who have received high-dose bisphosphonate (BP) or denosumab (Dmab) have not yet been established. Tooth extraction after starting medication has been believed to be a major risk factor for MRONJ, and therefore this procedure tends to be avoided. This study investigated the risk factors for MRONJ, with a special reference to the correlation between tooth extraction and development of MRONJ. One hundred and thirty-five cancer patients who were administrated high-dose BP or Dmab were enrolled in the study. Demographic factors, general condition, treatment factors, and dental findings were examined retrospectively using medical records and panoramic X-ray findings. The cumulative occurrence rate of MRONJ was calculated using the Kaplan–Meier method, and the correlation between these variables and development of MRONJ was analyzed by univariate and multivariate Cox regression analysis. MRONJ developed in 18 of 135 patients. The 1-, 2-, and 3-year cumulative occurrence rates were 8.6%, 21.5%, and 29.2%, respectively. The duration of medication before first visit to the dental unit and the presence of a tooth with clinical symptoms were significantly correlated with the development of MRONJ. The rate of MRONJ occurrence in patients who had teeth with clinical symptoms, but who did not undergo tooth extraction, became higher 2 years later than that in patients who underwent extraction of teeth with symptoms, although not significant. Early dental examination and effective preventative care to avoid infection/inflammation are important for preventing MRONJ.

Treatment modalities and risk factors associated with refractory neurosensory disturbances of the inferior alveolar nerve following oral surgery: a multicentre retrospective study

Little research has been conducted into hypoesthesia, and no studies have elucidated the risk factors for refractory hypoesthesia and compared treatment modalities. The purpose of this multicentre retrospective cohort study was to investigate the relationships between various risk factors, treatment modalities, and refractory hypoesthesia. Risk factors for refractory hypoesthesia after oral surgery were evaluated using univariate and multivariate analysis. To minimize the selection bias associated with a retrospective data analysis, a propensity score analysis was performed between the medication and non-medication groups (65 sites in each group). Moderate or severe hypoesthesia (odds ratio 13.42) and no or late administration of ATP/vitamin B12 (odds ratio 2.28) were significantly associated with refractory hypoesthesia. In the propensity score analysis, the incidence rate of refractory hypoesthesia in the medication group was lower than that in the non-medication group (P<0.001). This study demonstrated the multivariate relationships between various risk factors, treatment modalities, and refractory hypoesthesia. Moderate or severe hypoesthesia and no or late administration of ATP/vitamin B12 were significantly associated with refractory hypoesthesia. Therefore, clinicians should consider these risk factors and initiate early oral administration of ATP/vitamin B12 in cases of hypoesthesia.

Proper oral hygiene protocols decreased inflammation of gingivitis in a patient during chemotherapy with bevacizumab: a case report

The case is a woman who had a diagnosis of ovarian cancer and endometrial cancer. After surgical therapy, platinum‐based adjuvant treatment was performed, followed by additional bevacizumab administration. Because considerable gingivitis appeared, a proper approach for oral hygiene was performed. As a result, the symptom was reduced considerably.