Leucine-rich alpha-2-glycoprotein 1 affects bone destruction via IL-6 in mouse periodontitis model.

OBJECTIVE: To investigate the production of leucine-rich α-2-glycoprotein-1 (LRG1) in periodontitis patients and its effectiveness as a new diagnostic marker for periodontitis. SUBJECTS AND METHODS: In vitro experiments were conducted to analyze LRG1 mRNA expression in human gingival epithelial cells and fibroblasts via quantitative real-time PCR. In vivo experiments were conducted to analyze LRG1 localization in periodontitis patients. The correlation between the serum LRG1 levels and alveolar bone resorption in the mouse periodontitis model was also investigated. RESULTS: A positive correlation existed between the periodontal inflamed surface area and serum LRG1 levels (Spearman's rank correlation coefficient: 0.60). LRG1 mRNA expression in human gingival epithelial cells and fibroblasts was upregulated by Porphyromonas gingivalis stimulation or tumor necrosis factor-α stimulation. Interleukin-6 in human gingival epithelial cells and fibroblasts induced the production of LRG1 and transforming growth factor-ß. LRG1 levels in the periodontal tissue and serum in the periodontitis model were higher than those in control mice. LRG1 local administration resulted in alveolar bone resorption, whereas the administration of interleukin-6R antibody inhibited bone resorption. CONCLUSIONS: LRG1 levels in serum and periodontal tissue are upregulated in periodontitis and are implicated in periodontal tissue destruction through interleukin-6 production.

Analysis of Oral and Gut Microbiome Composition and Its Impact in Patients with Oral Squamous Cell Carcinoma.

The impact of gut and oral microbiota on the clinical outcomes of patients with oral squamous cell carcinoma (OSCC) is unknown. We compared the bacterial composition of dental plaque and feces between patients with OSCC and healthy controls (HCs). Fecal and dental plaque samples were collected from 7 HCs and 18 patients with OSCC before treatment initiation. Terminal restriction fragment-length polymorphism analysis of 16S rRNA genes was performed. Differences in bacterial diversity between the HC and OSCC groups were examined. We compared the occupancy of each bacterial species in samples taken from patients with OSCC and HCs and analyzed the correlation between PD-L1 expression in the tumor specimens and the occupancy of each bacterial species. The gut and oral microbiota of patients with OSCC were more varied than those of HCs. Porphyromonas and Prevotella were significantly more abundant in patients with OSCC than in HCs. The abundance of Clostridium subcluster XIVa in the gut microbiota of the PD-L1-positive group was significantly greater than that in the PD-L1-negative group. The oral and gut microbiomes of patients with OSCC were in a state of dysbiosis. Our results suggest the possibility of new cancer therapies targeting these disease-specific microbiomes using probiotics and synbiotics.

Assessment of Serum IgG Titers to Various Periodontal Pathogens Associated with Atrial Fibrillation in Acute Stroke Patients.

OBJECTIVES: There is accumulating evidence that periodontal disease is associated with atrial fibrillation (AF) or stroke, but it is unclear which causative species of periodontal disease are present in stroke patients with AF. We aimed to investigate the associations between AF and specific periodontal pathogens using serum titers of IgG antibodies of bacteria in acute stroke patients. MATERIALS AND METHODS: Acute stroke patients were registered at two hospitals. Serum samples were evaluated for titers of antibodies against 9 periodontal pathogens (16 genotypes) using ELISAs. We identified AF in patients according to the following criteria: (1) a history of sustained or paroxysmal AF or (2) AF detection upon arrival or during admission. We carried out propensity score matching to categorize the patients as those with AF and those without. RESULTS: Of the 664 acute stroke patients, 123 (18.5%) had AF. After propensity score matching, 234 patients were selected. Patients with AF had a higher prevalence of positive serum titers of antibodies against Porphyromonas gingivalis (FimA type III) and Porphyromonas gingivalis (FimA type V) than those without AF (59.0% vs. 39.3%, p=0.004 and 58.2% vs. 40.2%, p=0.009, respectively). CONCLUSIONS: Porphyromonas gingivalis, especially FimA type III and type V, might be associated with AF in stroke patients.

Periodontitis and the outcome of atrial fibrillation ablation: Porphyromonas gingivalis is related to atrial fibrillation recurrence.

INTRODUCTION: Inflammation is one of the main causes of atrial fibrillation (AF) recurrence after ablation. Porphyromonas gingivalis is a key periodontal pathogen in the oral-systemic disease connection and serum immunoglobulin G (IgG) antibody titers against P. gingivalis reflect the clinical status of periodontitis. This study aimed to investigate the relationship between late recurrence of AF after radiofrequency catheter ablation (RFCA) and serum IgG antibody titers against P. gingivalis. METHODS: A total of 596 AF patients (mean age, 64.9 ± 10.0 years; 69% male; 61% paroxysmal AF) who underwent a first session of RFCA were enrolled. Patients were carefully examined for late recurrence during a mean follow-up period of 17.1 ± 14.5 months. Serum IgG antibody titers against P. gingivalis (types I-IV) were measured using enzyme-linked immunosorbent assay. The results of serum antibody titers were divided into a high-value and a low-value group. RESULTS: Among the five P. gingivalis subtypes, serum antibody titer against P. gingivalis type IV was associated with late recurrence (odds ratio, 1.937; 95% confidence interval [CI], 1.301-2.884; p = .002). Multivariate Cox proportional-hazards regression analysis revealed that high-value serum antibody titer against P. gingivalis type IV independently predicted late recurrence (paroxysmal AF: adjusted hazard ratio [HR], 1.569; 95% CI, 1.010-2.427; p = .04; non-paroxysmal AF: adjusted HR, 1.909; 95% CI, 1.213-3.005; p = .004). CONCLUSION: Periodontitis was related to the late recurrence of AF after RFCA. P. gingivalis type IV may be pathogenic for AF recurrence after RFCA.

Porphyromonas gingivalis and left atrial appendage spontaneous echo contrast in atrial fibrillation ablation candidates.

Atrial fibrillation (AF) is associated with a fivefold risk of stroke and thrombotic embolism, which are usually derived from the left atrial appendage (LAA). Spontaneous echo contrast (SEC) is known as a risk factor for thrombosis. Porphyromonas gingivalis (P. gingivalis) has some prothrombotic effects and plays a key role in periodontitis and oral-systemic disease connection. We aimed to clarify the relationship between P. gingivalis and LAA SEC among AF patients. A total of 569 AF ablation candidates were enrolled in the present study. LAA SEC was categorized into nondense SEC and dense SEC based on transesophageal echocardiography. Serum immunoglobulin G antibody titers of P. gingivalis fimA subtypes (types I-IV) were measured with an enzyme-linked immunosorbent assay. The levels of antibody titers were categorized into high (> mean + 3 standard deviation) and low values. A total of 513 (90%) patients were included in the nondense SEC group, and 56 (10%) were included in the dense SEC group. Multivariate regression analysis revealed that the high-value serum antibody titers of P. gingivalis types II and IV were independently associated with dense SEC [type II: adjusted odds ratio (OR) 2.220; 95% confidence interval (CI) 1.062-4.643; P = 0.02; and type IV: adjusted OR 3.169; 95% CI 1.058-6.657; P = 0.002]. The results revealed that P. gingivalis types II and IV are related to LAA SEC severity among AF patients who receive appropriate anticoagulation therapy.

Prevalence of Torus Mandibularis in Young Healthy Dentate Adults.

PURPOSE: There have been only a few reports on the prevalence of torus mandibularis (TM) in young adult patients, and TM can have various adverse effects on oral and occlusal states in middle-age patients. This study was designed to determine the association between TM status and oral and occlusal states in young healthy dentate adults. MATERIALS AND METHODS: This was a cross-sectional study; the sample population included students at Hiroshima University (Hiroshima, Japan) who participated for practical education. The predictor variables in this study included oral symptoms (temporomandibular joint noise, tooth clenching and grinding, buccal mucosa ridging, dental attrition, and tongue habit), oral anatomy (occlusal vertical dimension), and oral function (average occlusal pressure, occlusal contact area, and maximum voluntary tongue pressure). The outcome variable was TM status (present or absent). Additional variables were demographic in nature and included age, number of residual teeth, body weight, and gender. These variables were compared among participants with and without TM using univariate analysis and multiple logistic regression analysis. Statistical analyses were carried out using SPSS Statistics 19 for Windows (IBM Corp, Armonk, NY); a P value less than .05 was considered significant. RESULTS: Of 204 participants included in the study, 50% were men and 50% were women. The mean age was 22.4 ± 2.7 years. TM was present in 119 (58.3%). Multiple logistic regression analysis showed that TM status was associated with dental attrition and occlusal contact area (P < .05). CONCLUSIONS: This study showed that TM was present in more than half the young healthy dentate participants and was closely associated with dental attrition and occlusal contact area. This study will provide readers with useful information to help prevent the development of TM before middle age.

Transformation of an odontogenic keratocyst into a solid variant of odontogenic keratocyst/keratoameloblastoma during long­term follow­up: A case report.

Keratoameloblastoma (KA) and solid variant of odontogenic keratocyst (SOKC) are rare odontogenic lesions, and their relationship and differences are unclear. The present study described a case that started as an odontogenic keratocyst (OKC) and transformed to SOKC/KA upon recurrence. Briefly, a 26­year­old man presented with swelling in the right cheek and was referred to the Department of Oral and Maxillofacial surgery, Hiroshima University Hospital (Hiroshima, Japan). At the initial visit, unicystic bone permeation was observed extending from the right canine to the molar, maxillary sinus and nasal cavity. After the biopsy, the patient underwent excisional surgery and was diagnosed with OKC. Thereafter, the lesion recurred six times over a period of 13 years and showed different histopathological features from those of the primary lesion, all consisting of numerous cysts with keratinization, which were diagnosed as SOKC/KA. The Ki­67 positivity rate was ~10%, which was higher than that of the primary lesion, but there was no atypia. Genetic analysis of the recurrent lesion revealed mutations in adenomatous polyposis coli and Kirsten rat sarcoma viral oncogene homolog. This case originated from OKC, and the morphological features of OKC and KA were mixed upon recurrence, supporting the commonality and association between the two. However, multiple mutations different from those of OKC and ameloblastoma were detected, suggesting an association of SOKC/KA with increased proliferative activity and a high recurrence rate.

Periodontal Treatment During the Blanking Period Improves the Outcome of Atrial Fibrillation Ablation.

BACKGROUND: Periodontitis has not been recognized as a modifiable risk factor for atrial fibrillation (AF). This prospective nonrandomized study investigated whether periodontal treatment improves the AF ablation outcome. METHODS AND RESULTS: We prospectively enrolled 288 AF patients scheduled to undergo initial radiofrequency catheter ablation. Each patient underwent periodontal inflamed surface area (PISA; a quantitative index of periodontal inflammation) measurement. All eligible patients were recommended to receive periodontal treatment within the blanking period, and 97 consented. During the mean follow-up period of 507±256 days, 70 (24%) AF recurrences were documented. Patients who exhibited AF recurrences had a higher PISA than those who did not (456.8±403.5 versus 277.7±259.0 mm2, P=0.001). These patients were categorized into high-PISA (>615 mm2) and low-PISA (<615 mm2) groups according to the receiver operating characteristic analysis for AF recurrence (area under the curve, 0.611; sensitivity, 39%; specificity, 89%). A high PISA, as well as female sex, AF duration, and left atrial volume, were the statistically significant predicter for AF recurrence (hazard ratio [HR], 2.308 [95% CI, 1.234-4.315]; P=0.009). In patients with a high PISA, those who underwent periodontal treatment showed significantly fewer AF recurrences (P=0.01, log-rank test). The adjusted HR of periodontal treatment for AF recurrence was 0.393 (95% CI, 0.215-0.719; P=0.002). CONCLUSIONS: Periodontitis may serve as a modifiable risk factor for AF. PISA is a hallmark of AF recurrence, and periodontal treatment improves the AF ablation outcome, especially for those with poor periodontal condition.

Effect of Periodontal Treatment on Reducing Chronic Inflammation in Systemically Healthy Patients With Periodontal Disease.

BACKGROUND: We determined the effects and an accurate marker of periodontal treatment on serum interleukin (IL)-6 and high-sensitivity C-reactive protein (HsCRP) levels in systemically healthy individuals with periodontal disease. METHODS: This multicenter study included systemically healthy individuals with periodontal disease who received initial periodontal treatment and had no periodontal treatment history. Periodontal parameters, including periodontal inflamed surface area, masticatory efficiency, and periodontal disease classification; serum IL-6 and HsCRP levels; and serum immunoglobulin (Ig)G titers against periodontal pathogens were evaluated at baseline and after treatment. Subjects were classified as low or high responders (group) based on periodontal inflamed surface area changes. RESULTS: There were 153 participants. Only periodontal inflamed surface area changes were markedly different between low and high responders. Periodontal treatment (time point) decreased both serum IL-6 and HsCRP levels. The interaction between group and time point was remarkable only for serum IL-6 levels. Changes in serum immunoglobulin (Ig)G titers against periodontal pathogens were not associated with IL-6 changes in high responders. We analyzed the indirect effect of serum anti-Porphyromonas gingivalis type 2 IgG titer changes using mediation analysis and found no significance. However, the direct effect of group (low or high responder) on IL-6 changes was considerable. CONCLUSIONS: Periodontal treatment effectively decreased serum IL-6 levels, independent of periodontal pathogen infection, in systemically healthy individuals with periodontal disease.

Relationship of oral bacterial number with medical hospitalization costs in analysis of Diagnosis Procedure Combination database from single institution in Japan.

Oral bacteria are known to be associated with perioperative complications during hospitalization. However, no presented reports have clarified the relationship of oral bacterial number with medical costs for inpatients. The Diagnosis Procedure Combination (DPC) database system used in Japan provides clinical information regarding acute hospital patients. The present study was conducted to determine the association of oral bacterial numbers in individual patients treated at a single institution with length of hospital stay and medical costs using DPC data. A total of 2369 patients referred by the medical department to the dental department at Hiroshima University Hospital were divided into the low (n = 2060) and high (n = 309) oral bacterial number groups. Length of hospital stay and medical costs were compared between the groups, as well as the associations of number of oral bacteria with Charlson comorbidity index (CCI)-related diseases in regard to mortality and disease severity. There was no significant difference in hospital stay length between the low (24.3 ± 24.2 days) and high (22.8 ± 20.1 days) oral bacterial number groups. On the other hand, the daily hospital medical cost in the high group was significantly greater (US$1456.2 ± 1505.7 vs. US$1185.7 ± 1128.6, P < 0.001). Additionally, there was no significant difference in CCI score between the groups, whereas the daily hospital medical costs for patients in the high group treated for cardiovascular disease or malignant tumors were greater than in the low number group (P < 0.05). Multivariate regression analysis was also performed, which showed that oral bacterial number, age, gender, BMI, cardiovascular disease, diabetes, malignant tumor, and hospital stay length were independently associated with daily hospitalization costs. Monitoring and oral care treatment to lower the number of oral bacteria in patients affected by cardiovascular disease or cancer may contribute to reduce hospitalization costs.

Skin Symptoms That Appeared after Fixation with a Titanium Plate in a Jaw Deformity Patient Suffering from Palmoplantar Pustulosis: A Case Report.

Palmoplantar pustulosis (PPP) is a stubborn skin disease involving repeated aseptic small pustules on the palms and soles of the feet, which is triggered and exacerbated by metals and dental focal infections. There are few reports of an exacerbation of PPP symptoms after orthognathic surgery. The patient is a 40-year-old female who consulted an orthodontist at our hospital, complaining of a protruding maxilla and malocclusion. Under the diagnosis of skeletal prognathism, she underwent surgery for jaw deformity. Although no allergic symptoms were observed during the orthodontic treatment prior to surgery, postoperative scaling on the palms and soles of her feet worsened, and itching was observed on the skin, especially on the titanium plate used to secure the bone fragments. Under the diagnosis of metal allergy, treatment with steroids and vitamin D ointment failed to improve the condition, so surgery was performed to replace the metal plate with a non-metallic absorbable plate in the third postoperative month. Afterwards, the pruritus resolved, and erythema and scale on the palms and soles nearly disappeared. In the present case, though, oral bacterial infection, a past history of smoking, and stress from surgery were also considered to be possible causes of PPP exacerbation, and we concluded that one of the causes of PPP exacerbation was metal allergy from the plates or screws used to fix the bone fragments.

A case report of allergic reaction with acute facial swelling: a rare complication of dental acrylic resin.

Resin components, such as methyl methacrylate (MMA) can cause allergic contact dermatitis (ACD). Allergic reactions to resin are usually delayed. Only a few studies have reported dental resin allergy with acute symptoms. Here, a case of ACD with acute facial swelling after dental treatment using resin material is reported. A 55-year-old woman with a history of periungual inflammation when using gel nail polish had repeated episodes of facial swelling after dental treatment with resin material. The resin temporary crown was removed, and symptoms were alleviated with antihistamines and corticosteroids. With the suspicion of resin allergy, skin tests were performed. Patch testing revealed positive reactions to self-adhesive resin cement (primer and polymerized), self-curing acrylic resin (liquid and polymerized), 2-hydroxyethyl methacrylate (2-HEMA), and ethylene glycol dimethacrylate (EGDMA), whereas the prick test was negative for all allergens. Complement C4 and C1 inhibitor activity were reference values in the tests for hereditary angioedema. Based on these findings, the patient was diagnosed with ACD to 2-HEMA and EGDMA. Since diagnosis, no similar symptoms have been observed in subsequent dental treatment with non-resin materials. The use of dental resin materials may cause ACD with an acute reaction. This report alerts dentists who routinely use resin materials.

Resting saliva volume as a risk factor for hypogeusia: A retrospective study.

OBJECTIVES: The causes of hypogeusia include zinc deficiency, systemic illness, and consumption of drugs. Notably, patients with oral cavity diseases such as oral candidiasis and salivary gland hypofunction may present with risk factors that remain unreported. Hence, this study aimed to investigate the relationship between age, sex, smoking status, serum zinc concentration, oral candidiasis, saliva volume, and taste function in patients with hypogeusia. SUBJECTS AND METHODS: Overall, 335 participants who complained of taste abnormalities underwent a taste test. Based on the recognition threshold value, the participants were classified as normal individuals (recognition threshold of 1 and 2) and patients with hypogeusia (recognition threshold of ≥3). The clinical characteristics, including resting saliva volume (RSV) and stimulated saliva volume (SSV), were compared, and a multivariate logistic regression analysis focusing on RSV was performed. RESULTS: Patients with hypogeusia had a lower RSV than normal individuals for all tastes, but not for SSV. Based on the results of regression analysis, RSV was identified as an independent predictor of hypogeusia for salty and bitter tastes. Moreover, the proportion of patients with decreased RSV increased as the number of taste qualities exceeding the reference recognition threshold increased. Furthermore, a decrease in RSV was associated with an increase in the recognition threshold for salty and bitter tastes. CONCLUSIONS: Based on the results of the present study, moisturizing the oral cavity may be useful against hypogeusia.

Impact of oral hygiene on febrile neutropenia during breast cancer chemotherapy.

PURPOSE: Oral hygiene is crucial in the management of oral and febrile complications during chemotherapy for cancer. This study aimed to investigate the impact of oral hygiene on the incidence of febrile neutropenia (FN) throughout the course of chemotherapy for breast cancer. METHODS: A total of 137 patients with breast cancer who underwent four cycles of adjuvant chemotherapy with docetaxel and cyclophosphamide (TC) combination therapy or docetaxel alone were assessed for oral hygiene by quantifying the number of oral bacteria they harbored. These patients received professional oral health care (POHC). Eighteen patients underwent primary prophylaxis with granulocyte colony-stimulating factors. The relationship between oral bacteria count and FN incidence was retrospectively assessed. RESULTS: The FN incidence rate was 47.4% throughout all treatment cycles (32.8%, 13.5%, 14.3%, and 14.4% in cycles 1, 2, 3, and 4, respectively). The oral bacteria count decreased with each treatment cycle (cycle 1: 9.10 × 106 colony-forming units (CFU)/mL, cycle 2: 5.89 × 106 CFU/mL, cycle 3: 4.61 × 106 CFU/mL, cycle 4: 5.85 × 106 CFU/mL, P = 0.004). Among 281 treatment cycles, FN occurred in 63 (22.4%). In the treatment cycle-based analysis, high oral bacteria count was an independent risk factor for FN. CONCLUSION: FN incidence decreased with each treatment cycle and was associated with changes in oral bacteria counts. The oral bacterial count was one of risk factors for FN development in breast cancer.

Porphyromonas gingivalis-odontogenic infection is the potential risk for progression of nonalcoholic steatohepatitis-related neoplastic nodule formation.

Porphyromonas gingivalis (P.g.), a major periodontal pathogen is a known risk factor for various systemic diseases. However, the relationship between P.g. and nonalcoholic steatohepatitis (NASH)-related hepatocellular carcinoma (HCC) is unclear. Thus, we aimed to elucidate whether P.g.-odontogenic infection promotes NASH-related HCC development/progression and to clarify its mechanism. Using high-fat diet (HFD)-induced NASH mouse model, P.g. was infected odontogenically. After 60 weeks of infection, tumor profiles were examined. Chow diet (CD) groups were also prepared at 60 weeks. Nodule formation was only seen in HFD-mice. P.g.-odontogenic infection significantly increased the mean nodule area (P = 0.0188) and tended to promote histological progression score after 60 weeks (P = 0.0956). Interestingly, P.g. was detected in the liver. HFD-P.g. (+) showed numerous TNF-α positive hepatic crown-like structures and 8-OHdG expression in the non-neoplastic liver. In P.g.-infected hepatocytes, phosphorylation of integrin ß1 signaling molecules (FAK/ERK/AKT) was upregulated in vitro. In fact, total AKT in the liver of HFD-P.g. (+) was higher than that of HFD-P.g. (-). P.g.-infected hepatocytes showed increased cell proliferation and migration, and decreased doxorubicin-mediated apoptosis. Integrin ß1 knockdown inhibited these phenotypic changes. P.g.-odontogenic infection may promote the progression of neoplastic nodule formation in an HFD-induced NASH mouse model via integrin signaling and TNF-α induced oxidative DNA damage.

Impact of Maximum Tongue Pressure in Patients with Jaw Deformities Who Underwent Orthognathic Surgery.

Malocclusion and morphological abnormalities of the jawbone often affect the stomatognathic function and long-term postoperative stability in patients with jaw deformities. There are few reports on the effect of maximum tongue pressure (MTP) in these patients. We investigated the relationship between the MTP and jawbone morphology and the effect of the MTP on surgery in 42 patients with jaw deformity who underwent surgical orthodontic treatment at Hiroshima University Hospital. The MTP was measured using a tongue pressure measurement device; the average value was considered as the MTP. Based on the MTP measured before surgery, patients were classified into the high- or the low-MTP group. The clinical findings and results of the cephalometric analysis were compared. Posterior movement of the mandible in the high-MTP group was significantly lower than that in the low-MTP group. The ANB angle, overjet, and overbite in the high-MTP group were significantly smaller than those in the low-MTP group. On the other hand, there was no difference between the two groups in the measured values, indicating a labial inclination of the anterior teeth (U1 to SN, U1 to FH, IMPA, and FMIA). MTP has been suggested to affect mandibular prognathism in patients with jaw deformities.

Masticatory dysfunction in patients with diabetic neuropathy: A cross-sectional study.

INTRODUCTION: Chewing well is essential for successful diet therapy and control of blood glucose level in patients with diabetes. In addition, long-term hyperglycemia is a risk factor for microvascular complications, which are the main cause of morbidity and mortality in these patients. Hence, it is plausible that masticatory disorder may be relevant to diabetic microvascular complications which is caused by long-term hyperglycemia. The aim of this study was to investigate whether masticatory disorders are relevant to diabetic microvascular complications. METHODS: This cross-sectional study included 172 patients with type 2 diabetes who underwent educational hospitalization in the Department of Endocrinology and Diabetic Medicine, Hiroshima University Hospital, from April 2016 to March 2020. Masticatory efficiency was determined quantitatively by using the GLUCO SENSOR GS-Ⅱ. Multivariable linear regression models were constructed to examine which factors were related to masticatory efficiency. Statistical significance was defined as a two-sided p value of < 0.05. RESULTS: According to the bivariable analysis, masticatory efficiency was significantly correlated with duration of diabetes (p = 0. 049), number of remaining teeth (p < 0.0001), the number of moving teeth (p = 0.007) and condition of diabetic neuropathy (p < 0.0001). Moreover, the number of remaining teeth (p < 0.0001) and diabetic neuropathy (p = 0.007) remained significantly correlated with masticatory efficiency in the multivariable analysis. CONCLUSIONS: For the first time, we demonstrated that patients with type 2 diabetes who developed diabetic neuropathy had significantly reduced masticatory efficiency. Effective mastication is an important factor in successful diet therapy for diabetes. To prevent the progression of diabetic complications, especially in patients with diabetic neuropathy, it may be necessary to combine individualized therapies from dentists and nutritionists with consideration for the level of masticatory dysfunction.

Serum IgG titers against periodontal pathogens are associated with cerebral hemorrhage growth and 3-month outcome.

To assess the influence of periodontal disease on cerebral hemorrhage and its clinical course, we examined the association of the serum IgG titer of periodontal pathogens with hemorrhage growth and 3-month outcome. We consecutively enrolled 115 patients with acute cerebral hemorrhage (44 females, aged 71.3 ± 13.1 years) and used ELISA to evaluate the serum IgG titers of 9 periodontal pathogens: Porphyromonas gingivalis, Aggregatibacter (A.) actinomycetemcomitans, Prevotella intermedia, Prevotella nigrescens, Fusobacterium (F.) nucleatum, Treponema denticola, Tannerella forsythensis, Campylobacter rectus, and Eikenella corrodens. Significant hematoma growth was defined as an increase in the volume of >33% or an absolute increase in the volume of >12.5 mL. A poor outcome was defined as a 3 or higher on the modified Rankin Scale. We observed hemorrhage growth in 13 patients (11.3%). Multivariate analysis revealed that increased IgG titers of A. actinomycetemcomitans independently predicted the elevated hemorrhage growth (odds ratio 5.26, 95% confidence interval 1.52-18.25, p = 0.01). Notably, augmented IgG titers of F. nucleatum but not A. actinomycetemcomitans led to a poorer 3-month outcome (odds ratio 7.86, 95% confidence interval 1.08-57.08, p = 0.04). Thus, we demonstrate that elevated serum IgG titers of A. actinomycetemcomitans are an independent factor for predicting cerebral hemorrhage growth and that high serum IgG titers of F. nucleatum may predict a poor outcome in patients with this disease. Together, these novel data reveal how systemic periodontal pathogens may affect stroke patients, and, should, therefore, be taken into consideration in the management and treatment of these individuals.

Association between periodontal disease due to Campylobacter rectus and cerebral microbleeds in acute stroke patients.

Oral health conditions and cerebral small vessel disease, such as white matter lesions or cerebral microbleeds (CMBs), are associated with the incidence of stroke. The purpose of this study was to examine the associations between oral health conditions (serum IgG titers of periodontal pathogens) with the presence or severity of CMBs in acute stroke patients. From January 2013 to April 2016, acute stroke patients were registered in two hospitals. Serum samples were evaluated for antibody titers against 9 periodontal pathogens using the ELISA method. The cut-off points for reactivity (the positive decision point) to each antigen were defined as more than a mean ELISA unit + 1 standard deviation (after logarithmic transformation) in all subjects. CMBs were evaluated on T2*-weighted MRI. In all, 639 patients were evaluated (ischemic, n = 533 and hemorrhagic, n = 106; 73.1 ± 12.9 years old). Among these patients, 627 were available for CMB evaluation. Among the 9 evaluated periodontal pathogens, only Campylobacter rectus (C. rectus) was associated with the presence of CMBs. the prevalence of positive serum antibody titers against C. rectus was higher among patients with CMBs than among those without CMBs (14.6% vs. 8.7%, P = 0.025). In addition, positive serum antibody titers against C. rectus remained one of the factors associated with the presence of CMBs in multivariate logistic analysis (odds ratio 2.03, 95% confidence interval 1.19-3.47, P = 0.010). A positive serum antibody titer against C. rectus was associated with the presence of CMBs in acute stroke patients.

Serum IgG titers to periodontal pathogens predict 3-month outcome in ischemic stroke patients.

Several cohort studies have shown that periodontal disease is associated with an increased risk for stroke. However, it remains unclear whether serum antibody titers for a specific periodontal pathogen are associated with outcome after ischemic stroke, and which kinds of pathogens are associated with ischemic stroke. We examined the relationship between serum IgG titers to periodontal pathogens and outcome in ischemic stroke patients. A total of 445 patients with acute ischemic stroke (194 female [44.0%], mean age 71.9±12.3 years) were registered in this study. Serum IgG titers to 9 periodontal pathogens (Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Prevotella intermedia, Prevotella nigrescens, Fusobacterium nucleatum, Treponema denticola, Tannerella forsythensis, Campylobacter rectus, Eikenella corrodens) were evaluated using the enzyme-linked immunosorbent assay (ELISA) method. An unfavorable outcome was defined as a 3 or higher on the modified Rankin Scale. The proportion of patients with unfavorable outcome was 25.4% (113 patients). Based on multivariate logistic regression analysis, numbers of IgG antibodies positive for periodontal pathogens (odds ratio 1.20, 95% CI 1.02-1.41, p = 0.03) were independent predictors of unfavorable outcome in ischemic stroke patients.