The Predictive Value of Interleukin-6 and Neutrophil-Lymphocyte Ratio in Patients with Severe and Extremely Severe Oral and Maxillofacial Space Infections.

OBJECTIVE: To investigate the correlation between clinical manifestation and neutrophil-lymphocyte ratio, C-reactive protein (CRP), and interleukin-6 (IL-6) in the patients with severe and extremely severe oral and maxillofacial space infection (OMSI). METHODS: In this retrospective study, we included 18 patients with severe and extremely severe OMSI from November 2012 to October 2018. Pearson or Spearman correlation coefficients were calculated to measure the association between the number of complications and locations and the number and percentage of lymphocyte, leukocyte, neutrophil, eosinophil, basophil, monocyte, CRP, and IL-6. A multivariable regression model was used to predict the number of complications and locations from these measures. RESULTS: IL-6 was positively correlated with neutrophil-lymphocyte ratio (r s = 0.773, P = 0.005), percentage of neutrophil (r s = 0.927, P = 0.001), and the number of neutrophil (r s = 0.627, P = 0.039). It was negatively correlated with percentage of monocyte (r s = -0.773, P = 0.005). CRP was positively correlated with neutrophil-lymphocyte ratio (r s = 0.556, P = 0.020) and percentage of neutrophil (r s = 0.515, P = 0.035). It was negatively correlated with the number of lymphocyte (r s = -0.517, P = 0.017), percentage of lymphocyte (r s = -0.578, P = 0.015), number of eosinophil (r s = -0.560, P = 0.020), percentage of eosinophil (r s = -0.504, P = 0.039), number of basophil (r s = -0.504, P = 0.039), and percentage of basophil (r s = -0.548, P = 0.023). The number of the involved organs was positively correlated with neutrophil-lymphocyte ratio (r s = 0.511, P = 0.030). The number of complications was positively correlated with the percentage of neutrophils (r = 0.738, P = 0.001), the neutrophil-lymphocyte ratio (r = 0.576, P = 0.012), IL-6 (r s = 0.907, P = 0.001), and CRP (r s = 0.599, P = 0.011). Multivariable regression analysis showed that the neutrophil-lymphocyte ratio (ß = 0.080) was a significant predictor of the number of the involved organs and the neutrophil-lymphocyte ratio (ß = 0.099). In addition, IL-6 (ß = 0.002) was a significant predictor of the number of complications. CONCLUSIONS: The neutrophil-lymphocyte ratio and IL-6 contributed to the assessment of general condition in severe and profound OMSI patients. These parameters can be used as predictors to evaluate the severity of OMSI.

What can we learn about functional importance of human antimicrobial peptide LL-37 in the oral environment from severe congenital neutropenia (Kostmann disease)?

The human antimicrobial peptide LL-37 is produced by neutrophils and epithelial cells, and the peptide can be detected in plasma as well as saliva. LL-37 is active against both gram-positive and gram-negative bacteria including oral pathogens such as Porphyromonas gingivalis and Streptococcus mutans. Besides its antimicrobial properties, LL-37 modulates the innate immune system, and furthermore, it also affects host cell viability. Although, both structural and functional properties of LL-37 have been extensively investigated, its physiological/pathophysiological importance in-vivo is not completely understood. In this review, Kostmann disease (morbus Kostmann) is highlighted since it may represent a LL-37 knockdown model which can provide new important information and insights about the functional role of LL-37 in the human in-vivo setting. Patients with Kostmann disease suffer from neutropenia, and although they are treated with recombinant granulocyte colony-stimulating factor (G-CSF) to normalize their levels of neutrophils, they lack or have very low levels of LL-37 in plasma, saliva and neutrophils. Interestingly, these patients suffer from severe periodontal disease, linking LL-37-deficiency to oral infections. Thus, LL-37 seems to play an important pathophysiological role in the oral environment antagonizing oral pathogens and thereby prevents oral infections.

Significantly higher frequencies of hematinic deficiencies and hyperhomocysteinemia in oral precancer patients.

BACKGROUND/PURPOSE: Our previous studies found relatively higher frequencies of anemia, hematinic deficiencies, and hyperhomocysteinemia in patients with different types of oral mucosal diseases. This study evaluated whether patients with oral precancerous lesions (oral precancer patients) had significantly higher frequencies of anemia, hematinic deficiencies, and hyperhomocysteinemia than healthy control subjects. METHODS: The complete blood count, serum iron, vitamin B12, folic acid, and homocysteine levels in 131 oral precancer patients including 96 oral leukoplakia, 26 oral erythroleukoplakia, and 9 oral verrucous hyperplasia patients and in 131 age- and sex-matched healthy control subjects were measured and compared. RESULTS: We found significantly lower mean serum iron (for women only), vitamin B12, and folic acid levels and a significantly higher mean serum homocysteine level in oral precancer patients than in healthy control subjects (all P-values < 0.05). Moreover, 131 oral precancer patients had significantly higher frequencies of blood hemoglobin (3.1%), vitamin B12 (43.5%), and folic acid (46.6%) deficiencies and hyperhomocysteinemia (22.1%) than 131 healthy control subjects (all P-values < 0.05). Of 131 oral precancer patients, lower mean serum folic acid levels were found in 87 cigarette smokers than in 44 non-smokers (P = 0.002), in 26 smokers consuming > 20 cigarettes per day than in 61 smokers consuming ≤ 20 cigarettes per day (P = 0.024), and in 52 betel quid chewers than in 79 non-chewers (P = 0.051). CONCLUSION: There are significantly higher frequencies of anemia, serum vitamin B12, and folic acid deficiencies, and hyperhomocysteinemia in oral precancer patients than in healthy control subjects.

Correlation analysis on serum inflammatory cytokine level and neurogenic pulmonary edema for children with severe hand-foot-mouth disease.

OBJECTIVE: This study aims to discuss the correlation between serum inflammatory cytokines and neurogenic pulmonary edema (NPE) in children with severe hand-foot-mouth disease (HFMD). METHODS: A total of 89 patients with severe HFMD were enrolled into this study. These patients were divided into two groups, according to the presence of NPE: central nervous system disease (CNSD) group and NPE group. Serum IL-4, IL-10, IL-6, IL-17, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) levels were measured in patients by enzyme-linked immunosorbent assay at 1, 3, and 5 days after admission. Furthermore, risk factors for NPE were screened using multivariable logistic regression analysis. RESULTS: IL-6, TNF-α, IL-10, and interferon-γ (IFN-γ) levels in the NPE group were higher than in the CNSD group. TNF-α, IL-10, and IFN-γ levels reached a peak on the 3rd day of admission. Age, continuous fever, blood sugar, white blood cell count, and IL-10 were risk factors for the occurrence of NPE in severe HFMD. CONCLUSION: The dynamic unbalance of inflammatory cytokines is related to the occurrence and progress of NPE.

[The mouth of patients with acromegaly]. / La bouche de l'acromégale.

Orofacial changes are frequent in acromegaly. Their evolution is slowly progressive. The lips (everted and thickened), the mandibular morphology (prognathism), the tongue (macroglossia), the soft palate and the uvula (increased and thickened), the parodontis (gingival hyperplasia, paradontitis), the teeth (increased interdental spaces, hypercementosis, increased dental mobility, multiple tooth loss) are concerned. Functional consequences are significant (obstructive sleep apnea syndrome, malocclusion, pain of the oral maxillofacial area, decrease of the quality of life). They are rarely noticed as the first symptoms of the disease and rarely responsible for the diagnosis of acromegaly because of a progressive development over a long period of time, and because of the low prevalence of the disease which can be unknown by dentists and dental surgeons. When patients are cured or well-controlled, abnormalities of soft tissues improve but are not always completely reversible and bone enlargement remain unchanged. If any corrective surgical procedures are to be performed, this should be carried out only after normalization of GH and IGF I levels.

Sialic acid as a biomarker of oral potentially malignant disorders and oral cancer.

BACKGROUND: Carcinogenesis is a multistep process where a healthy cell has initially a precancerous stage and finally an early cancerous stage. The process of carcinogenesis can be divided into three stages of initiation, promotion, and progression. In this process, there is increased turnover, secretion, and/or shedding from malignant cells. Glycoproteins like sialic acid are expressed on the cell surface. In oral potentially malignant disorders (OPMDs) and oral cancer (OC), the sialic acid level is seen to increase due to high cell turnover and shedding of malignant cells which, in turn, results in the release of glycoproteins like sialic acid into circulation. Glycoproteins also form an important constituent of salivary mucins and hence due to the same mechanism, an increase in sialic acid level is also seen in saliva. OBJECTIVE: The aim is to estimate serum and salivary sialic acid levels in healthy controls, patients with OPMDs and patients with OC. MATERIALS AND METHODS: In this observational cross-sectional study, serum and salivary sialic acid levels were estimated in thirty healthy controls, thirty patients with OPMDs and thirty patients with OC. RESULTS: Serum and salivary sialic acid levels obtained were subjected to statistical analysis. Post hoc Tukey test was used to compare the serum and salivary sialic acid levels of the two study groups to the control group. ANOVA test was used for the comparison of sialic acid levels between the groups. Pearson's correlation coefficient was used to assess correlation (P < 0.05 was considered statistically significant). The mean serum and salivary sialic acid levels were increased significantly in subjects with OPMDs and OC when compared to healthy controls. CONCLUSION: This study highlights the high expression of sialic acid on outer cell membranes, due to the significant increase in subjects with OPMDs and OC when compared to healthy controls. A significant increase in sialic acid level is also seen in saliva. Hence, it can be stated that saliva can be used as a reliable, noninvasive tool in diagnosis and management of OPMDs and OC.

[The oral cavity: A mirror of diabetes]. / La bouche : un miroir du diabète.

Diabetes and the oral cavity are closely associated as diabetes physiopathology affects the mouth and the oral manifestations are numerous and varied. These need to be searched systematically at every clinical examination as they are not only comorbidity factors but also have a two-way relationship with diabetes control. Periodontal diseases are the most frequent pathologies and the relationship with glycemic control has clearly been established: their frequency increases in case of uncontrolled glycemia, which makes them a good marker of glycated hemoglobin. Thorough oral health follow-up of diabetic patients that is coordinated by its various actors from the beginning of the treatment is thus of great interest. Most of the care given to diabetic patients can easily be performed at the dental clinic, provided adequate precautions are taken and improvement of the oral cavity is beneficial to glycemic control as well as to the patients' quality of life. When implemented by trained oral health professionals in dental clinics, therapeutic education proves highly efficient.

Increased oral inflammation, leukocytes, and leptin, and lower adiponectin in overweight or obesity.

OBJECTIVES: The association between body mass index (BMI) and oral diseases was investigated, and levels of obesity-related inflammatory mediators were evaluated. SUBJECTS AND METHODS: Participants (n = 160) were clinically and radiographically examined for oral diseases. Blood profiles were recorded. Levels of adiponectin, leptin, and C-reactive protein (CRP) were measured. RESULTS: One hundred and thirteen (70.6%) participants had overweight or obese status (BMI ≥ 23.0 kg/m2 ). Sum of dental diseases and severe periodontitis were higher in overweight or obese individuals than in normal-weight participants (p = .037 and p = .002, respectively). A significant difference in oral mucosal disorders between normal weight and overweight or obesity was not found. Plasma leukocyte counts, liver enzymes, leptin, and CRP levels were increased while adiponectin levels were decreased in individuals with BMI≥23.0 kg/m2 compared with normal-weight participants. After adjusting for age, sex, fasting plasma glucose level, smoking, and exercise, obesity was associated with sum of dental diseases (ß = 0.239, p = .013), severe periodontitis (OR=4.52; 95% CI 1.37, 14.95, p = .013), adiponectin (ß = -0.359, p < .001), leptin (ß = 0.630, p < .001), and CRP levels (OR=12.66; 95% CI 3.07, 52.21, p < .001). CONCLUSION: Overweight or obese Thai people were related to an increase in inflammatory dental and periodontal diseases with an altered health profile and plasma inflammatory mediators.

Anemia and hematinic deficiencies in gastric parietal cell antibody-positive and -negative oral mucosal disease patients with microcytosis.

BACKGROUND/PURPOSE: Microcytosis is defined as mean corpuscular volume (MCV) < 80 fL. This study assessed the anemia statuses and hematinic deficiencies in 30 patients with gastric parietal cell antibody-positive microcytosis (GPCA+/microcytosis) and 210 patients with GPCA-negative microcytosis (GPCA-/microcytosis). METHODS: We measured and compared the mean red blood cell (RBC) count, MCV, and RBC distribution width (RDW), as well as blood levels of hemoglobin, iron, vitamin B12, folic acid, and homocysteine among the aforementioned patient groups and 240 healthy controls. RESULTS: Compared with GPCA-/microcytosis, the positive counterparts presented with a lower mean serum vitamin B12 level (marginal significance), significantly higher mean RDW and serum homocysteine level, and significantly greater frequencies of vitamin B12 deficiency and high homocysteine level. GPCA-/microcytosis patients had significantly greater frequencies of hemoglobin, iron, vitamin B12, and folic acid deficiencies and of RBC count > 5 × 1012/L than healthy controls. Moreover, 19 of 30 GPCA+/microcytosis patients and 143 of 210 GPCA-/microcytosis patients had anemia, with iron deficiency anemia being the most common type, followed by thalassemia trait-induced anemia and microcytic anemia due to other causes. CONCLUSION: We conclude that GPCA in microcytosis patients' sera may have caused significantly lower mean vitamin B12 level as well as significantly higher mean RDW and serum homocysteine level in our GPCA+/microcytosis patients than in GPCA-/microcytosis patients. Herein, iron deficiency anemia was the most common type of anemia in anemic GPCA+/microcytosis and GPCA-/microcytosis patients.

Anemia and hematinic deficiencies in oral mucosal disease patients with microcytosis.

BACKGROUND/PURPOSE: Patients with microcytosis (defined as mean corpuscular volume < 80 fL) are not uncommonly found in oral mucosal disease clinics. This study assessed the anemia statuses and hematinic deficiencies in 240 oral mucosal disease patients with microcytosis. METHODS: The mean red blood cell (RBC) count, mean corpuscular volume, and RBC distribution width, as well as blood concentrations of hemoglobin (Hb), iron, vitamin B12, folic acid, and homocysteine in 240 microcytosis patients and in 240 age- and sex-matched healthy control individuals were measured and compared. RESULTS: Microcytosis patients had significantly lower mean Hb, iron, and folic acid levels as well as significantly higher mean RBC count and RBC distribution width than healthy control individuals. Microcytosis patients also had significantly greater frequencies of Hb, iron, vitamin B12, and folic acid deficiencies as well as of RBC number > 5 × 1012/L, and abnormally high homocysteine levels than healthy control individuals. Moreover, 162 (67.5%) of the 240 microcytosis patients had anemia. Of 162 anemic microcytosis patients, 87 (53.7%) had iron deficiency anemia, 61 (37.7%) had thalassemia trait (TT)-induced anemia, and 14 (8.6%) had other microcytic anemia. CONCLUSION: We conclude that approximately 45%, 4%, and 5% of microcytosis patients have iron, vitamin B12, and folic acid deficiencies, respectively, and approximately 10% of microcytosis patients have abnormally high homocysteine levels. Moreover, 67.5% of 240 microcytosis patients and 50.8% of 120 TT patients had anemia. Iron deficiency anemia is the most common type of anemia in microcytosis patients, followed by TT-induced anemia and other microcytic anemia.

Oral and vulvovaginal changes in pregnancy.

Physiologic alterations of the oral and vulvovaginal mucosal surfaces result from the profound hormonal and immunologic changes of gestation. High estrogen levels are responsible for the vascular changes noted on mucosal surfaces. Gingival hyperemia and edema, gingivitis and pyogenic granuloma are the most common alterations of the oral mucosa during gestation. Physiologic changes of the vulvovaginal area are mainly of vascular nature, and include among others varicose veins. The oral and vulvovaginal mucosal surfaces can be affected by diseases that can worsen or develop in pregnancy. Oral lesions are encountered in a large spectrum of diseases including aphthosis, pemphigus vulgaris, systemic lupus, and Behçet disease. Pregnancy dermatoses such as impetigo herpetiformis and gestational pemphigoid can exceptionally affect the oral mucosa. Infections of the vulvovaginal region by Candida species, Trichomononas vaginalis, human papilloma virus, and herpes simplex virus have been associated with fetal risks. The dermatologist, obstetric medicine physician, and neonatologist should be familiar with the above physiologic changes as well as maternal/fetal risks relevant to disease affecting these mucosal surfaces during gestation.

Correlation of serum ANA and direct immunofluorescence studies in elderly Thai patients with red and white oral lesions.

OBJECTIVES: This study investigated the presence of serum antinuclear antibodies (ANA) profile and direct immunofluorescence (DIF) evaluation in elderly Thai patients with red and white oral lesions. MATERIALS AND METHODS: Thirty-two patients with red and white oral lesions were divided into two groups: group I consisted of 10 cases not taking medications, while group II consisted of 12 cases taking medications, and 30 healthy subjects as a control group. Blood samples were used to determine the ANA profile. DIF was investigated in the lesion containing groups. RESULTS: Serum ANA was found in six cases (60%) in group I, eight cases (66.7%) in group II, and 19 cases (63.3%) in the control group. There were no significant differences between group I and group II and the control group (P > 0.05). Serum ANA was most commonly found in patients taking hypolipidemics (80%), followed by antihypertensives (71.4%), NSAIDs (50%), hypoglycemics (50%), and others (66.7%). The anticytoplasmic staining frequency in group II was higher compared with group I and the control group. Anti-dsDNA antibodies were not found in any group. CONCLUSIONS: Elderly patients with red and white oral lesions who were taking medications had a higher serum ANA frequency than group I and the control group.

Association of serum cytokines with oral HPV clearance.

BACKGROUND: Initial studies suggest higher serum levels of some pro-inflammatory cytokines may be associated with decreased cervical human papillomavirus (HPV) clearance. However, the relationship of cytokines with oral HPV clearance has not been explored. METHODS: From 2010 to 2014, oral rinse and serum samples were collected semi-annually from 1601 adults. Oral rinse samples were tested for HPV DNA using PCR. Based on oral HPV results, 931 serum samples were selected for cytokine evaluation to include a roughly equal number of prevalent (n=307), incident (n=313), and no oral HPV infections (n=311). Electrochemiluminescence multiplex assays were used to determine the concentrations of IL-6, IL-8, TNF-α, IFN-γ, IL-1ß, IL-2, IL-4, IL-10, IL-12 and IL-13. The relationship between serum cytokine concentrations (categorized into quartiles) and oral HPV clearance was evaluated with Wei-Lin-Weissfeld regression models, adjusting for HPV infection type (prevalent vs. incident), age, HIV status, and CD4 T cell count. RESULTS: Higher TNF-α concentration was associated with decreased clearance in men (highest vs. lowest quartile, adjusted hazard ratio [aHR]=0.52, 95% CI=0.34-0.79) and women (aHR=0.76, 95% confidence interval [CI]=0.55-1.04), with stronger associations in men than women (p-interaction=0.049). Higher IL-2 concentration was associated with reduced clearance in men (aHR=0.69, 95% CI=0.50-0.95), but not women (p-interaction=0.058). Results were similar within CD4 T cell strata (CD4⩾500 or CD4<500 cells/µl) among HIV-infected participants. No other cytokines were associated with clearance. CONCLUSION: High serum TNF-α is associated with reduced clearance of oral HPV infection.

Plasma endotoxin activity in kangaroos with oral necrobacillosis (lumpy jaw disease) using an automated handheld testing system.

The aim of the present study was to evaluate the reliability and effectiveness of directly determining endotoxin activity in plasma samples from kangaroos with lumpy jaw disease (LJD, n=15) and healthy controls (n=12). Prior to the present study, the ability of the commercially available automated handheld portable test system (PTS(TM)) to detect endotoxin activity in kangaroo plasma was compared with that of the traditional LAL-kinetic turbidimetric (KT) assay. Plasma samples, which were obtained from endotoxin-challenged cattle, were diluted 1:20 in endotoxin-free water and heated to 80°C for 10 min. The performance of the PTS(TM) was not significantly different from that of the traditional LAL-based assay. The data obtained using PTS(TM) correlated with those using KT (r(2)=0.963, P<0.001). These findings indicated that the PTS(TM) is applicable as a simplified system to assess endotoxin activity in macropods. In the present study, we demonstrated the diagnostic value of plasma endotoxin activity in kangaroos with systemic inflammation caused by oral necrobacillosis and identified plasma endotoxin activity as a sensitive marker of systemic inflammation in kangaroos with LJD. Based on ROC curves, we proposed a diagnostic cut-off point for endotoxin activity of >0.22 EU/ml for the identification of LJD. Our results indicate that the assessment of plasma endotoxin activity is a promising diagnostic tool for determining the outcome of LJD in captive macropods.

Serum and salivary IgG and IgA antibodies to desmoglein 3 in mucosal pemphigus vulgaris.

BACKGROUND: The use of saliva for the diagnosis of pemphigus vulgaris (PV) by enzyme-linked immunosorbent assay (ELISA) using desmoglein (Dsg)3 antigen has not been extensively documented, nor has the detection of serum IgA antibodies to Dsg3. OBJECTIVES: (i) To establish whether whole saliva might provide a suitable alternative to serum for diagnosing and monitoring PV; (ii) to investigate whether anti-Dsg3 IgA antibodies can be detected in serum and saliva and (iii) to establish whether there is an association between serum or saliva anti-Dsg3 antibodies and disease severity. METHODS: Precoated Dsg3 ELISA plates were used to test serum and/or saliva for IgG and IgA antibodies. Matched serum and whole saliva samples were collected from 23 patients with PV, 17 healthy subjects and 19 disease controls. All patients with PV, disease controls and six healthy controls provided matched parotid saliva. RESULTS: Whole saliva IgG antibodies to Dsg3 were detected in 14 of 23 patients (61%) and serum IgG antibodies were detected in 17 of 23 (74%) with a strong positive correlation. Serum IgA antibodies were detected in 14 of 23 patients with PV (61%) with a combined positivity (IgG and/or IgA antibodies to Dsg3) of 78% (18 of 23). We were unable to show IgA anti-Dsg3 antibodies in either whole or parotid saliva of patients with PV. Sequential samples showed that changes in IgG antibody titres in whole saliva were associated with a change in disease severity scores. CONCLUSIONS: Assay of salivary IgG antibodies to Dsg3 offers a diagnostic alternative to serum in the diagnosis and monitoring of PV. The role of anti-Dsg3 IgA antibodies requires further elucidation in the pathogenesis of PV.