Autoimmunity and epithelial dysplasia in patients with oral lichenoid diseases.

OBJECTIVES: The primary objective of this study was to explore relationship between autoimmunity and epithelial dysplasia in patients with oral lichenoid diseases. MATERIALS AND METHODS: A total of 66 patients with oral lichen planus (OLP), 35 with oral lichenoid lesion (OLL), and 85 with oral lichenoid drug reaction (OLDR) were enrolled. OLP, OLL, and OLDR were diagnosed following the definitions of the modified World Health Organization criteria, except for the absence of epithelial dysplasia. All patients underwent diagnostic incisional biopsy and adjunctive direct immunofluorescence assays. An indirect immunofluorescence assay was conducted to determine the antinuclear antibody (ANA) positivity. RESULTS: OLP and OLDR patients with epithelial dysplasia demonstrated higher prevalence of serum ANA positivity compared to those without epithelial dysplasia. Elevated serum levels of high sensitivity-C reactive proteins were observed in the OLP, OLL, and OLDR patients with epithelial dysplasia. In the DIF analysis, patients with epithelial dysplasia in the OLP exhibited a higher prevalence of C3 deposition in the basement membrane zone. CONCLUSIONS: This study proposed that autoimmunity may contribute to elevating levels of focal and chronic systemic inflammation, potentially influencing abnormal wound healing and development of dysplastic changes in the oral epithelium among patients with oral lichenoid disease.

Complex interplay of oral health, muscle and bone metabolism, and frailty in older individuals.

OBJECTIVES: To investigate molecular and clinical background of associations among oral health, muscle and bone metabolism, and frailty incidence in patients with fall and fracture history. MATERIALS AND METHODS: In total, 88 elderly participants (mean age 71.9 ± 5.8 years) with the distal radius fractures were included. Participants were divided into three groups based on an Oral Health Assessment Tool score. Fried criteria and Mini-nutritional assessments were adopted to diagnose frailty and malnutrition, respectively. Blood samples were collected and analyzed for serum levels of bone turnover markers, proteins, insulin-like growth factor-1, 25-hydroxyvitamin D, and inflammatory cytokines. The mRNA levels of markers of inflammation, muscle synthesis and wasting, and muscle homeostasis regulator in the pronator quadratus muscle were analyzed. RESULTS: Patients with deteriorated oral health demonstrated a higher prevalence of frailty and malnutrition. Significantly lower serum levels of total protein and higher concentrations of tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) were detected in patients with poor oral health. Significant interaction effects between oral health and frailty level in gait speed, serum TNF-α, IL-1ß, and total protein levels were exhibited. Significantly different mRNA expression levels in the pronator quadratus muscle of TNF-α, IL-1ß, NF kB, MYOG, and FOXO1 following the oral health were detected. CONCLUSION: This study highlights relationship between oral health, nutritional uptake, systemic inflammation, and their combined impact on muscle and bone metabolism, ultimately affecting frailty development in the aging populations. CLINICAL RELEVANCE: A comprehensive understanding of mutual interactions among oral health, nutrition, and inflammation is essential for managing frailty.

Machine-Learning Algorithms Using Systemic Inflammatory Markers to Predict the Oncologic Outcomes of Colorectal Cancer After Surgery.

BACKGROUND: This study aimed to investigate the clinical significance of machine-learning (ML) algorithms based on serum inflammatory markers to predict survival outcomes for patients with colorectal cancer (CRC). METHODS: The study included 941 patients with stages I to III CRC. Based on random forest algorithms using 15 compositions of inflammatory markers, four different prediction scores (DFS score-1, DFS score-2, DFS score-3, and DFS score-4) were developed for the Yonsei cohort (training set, n = 803) and tested in the Ulsan cohort (test set, n = 138). The Cox proportional hazards model was used to determine correlation between prediction scores and disease-free survival (DFS). Harrell's concordance index (C-index) was used to compare the predictive ability of prediction scores for each composition. RESULTS: The multivariable analysis showed the DFS score-4 to be an independent prognostic factor after adjustment for clinicopathologic factors in both the training and test sets (hazard ratio [HR], 8.98; 95% confidence interval [CI] 6.7-12.04; P < 0.001 for the training set and HR, 2.55; 95% CI 1.1-5.89; P = 0.028 for the test set]. With regard to DFS, the highest C-index among single compositions was observed in the lymphocyte-to-C-reactive protein ratio (LCR) (0.659; 95% CI 0.656-0.662), and the C-index of DFS score-4 (0.727; 95% CI 0.724-0.729) was significantly higher than that of LCR in the test set. The C-index of DFS score-3 (0.725; 95% CI 0.723-0.728) was similar to that of DFS score-4, but higher than that of DFS score-2 (0.680; 95% CI 0.676-0.683). CONCLUSIONS: The ML-based approaches showed prognostic utility in predicting DFS. They could enhance clinical use of inflammatory markers in patients with CRC.

Impact of Mitomycin-C-Induced Neutropenia after Hyperthermic Intraperitoneal Chemotherapy with Cytoreductive Surgery in Colorectal Cancer Patients with Peritoneal Carcinomatosis.

BACKGROUND: Mitomycin-C (MMC) is the most commonly used chemotherapeutic agent for hyperthermic intraperitoneal chemotherapy (HIPEC) after cytoreductive surgery (CRS). However, MMC has a side effect of myelosuppression. This study aimed to evaluate the clinical manifestations and impact of MMC-induced neutropenia after CRS and HIPEC in colorectal cancer patients. METHODS: A total of 124 colorectal cancer patients who underwent CRS with HIPEC between March 2015 and January 2019 were evaluated. Patients with malignancies of non-colorectal origin, hospital stay longer than 60 days, peritoneal cancer index > 30, and complete cytoreduction score > 2 were excluded. MMC 35 mg/m2 was administered for 90 min at 41-43 °C. The patients were divided into three groups: no neutropenia, mild neutropenia (grade 1-2), and severe neutropenia (grade 3-4). RESULTS: In total, mild and severe neutropenia occurred in 30 (24.2%) and 48 (38.7%) patients, respectively. Age and body surface area were significantly different among the neutropenia groups. Severe neutropenia developed significantly earlier than mild neutropenia (6.9 days vs. 10.4 days, p < 0.001) and also lasted significantly longer (4.6 days vs. 2.5 days, p = 0.005). The rate of major postoperative complications was significantly higher in the severe neutropenia group than in the no and mild neutropenia groups (8.3% vs. 6.7% vs. 6.5%, p = 0.015) CONCLUSIONS: Severe neutropenia starts earlier and lasts longer than mild neutropenia after CRS and HIPEC using an MMC triple method. The higher rate of major postoperative complications in patients with severe neutropenia highlights the importance of postoperative management during the neutropenia period.

Association of Albumin-Bilirubin Grade and Myosteatosis with its Prognostic Significance for Patients with Colorectal Cancer.

BACKGROUND: The albumin-bilirubin (ALBI) grade is a useful prognostic and predictive marker for patients with liver disease. Its clinical significance has been limited to patients with colorectal cancer (CRC). Furthermore, the association between the ALBI grade and skeletal muscle-related indices is unclear. METHODS: This study enrolled 1015 patients who underwent computed tomography (CT) scans within 31 days before surgery. The prognostic value of the ALBI grade in predicting overall survival (OS) was assessed using the Cox proportional hazards model. The correlation between the ALBI grade and the skeletal muscle index or radiodensity (myosteatosis) was evaluated. The predictive accuracy of ALBI alone and in combination with myosteatosis was compared using Harrell's concordance index (C-index). RESULTS: The significant prognostic factors for OS identified in the multivariable analysis were the ALBI group (low vs high: hazard ratio [HR], 1.566; 95 % confidence interval [CI], 1.174-2.089; p = 0.002) and myosteatosis (low vs. high: HR, 0.648; 95 % CI, 0.486-0.865; p = 0.003). The rate of low-grade myosteatosis increased as the ALBI grade increased. The C-index of combined ALBI and myosteatosis (0.650; 95 % CI, 0.618-0.683) was superior to that of ALBI alone (0.603; 95 % CI, 0.575-0.631; bootstrap incremental area under the curve [iAUC] mean difference, 0.047; 95 % CI, 0.012-0.070) and myosteatosis alone (0.608; 95 % CI, 0.577-0.640; bootstrap iAUC mean difference, 0.042; 95 % CI, 0.023-0.064). CONCLUSION: The ALBI grade is significantly associated with myosteatosis. The ALBI grade is a significant prognostic factor, and the combination of ALBI and myosteatosis show an additive value in discriminating survival of patients with CRC.

Potential Role of Obstructive Sleep Apnea on Pain Sensitization and Jaw Function in Temporomandibular Disorder Patients.

BACKGROUND: The relationships between obstructive sleep apnea (OSA) and diverse types of pain disorders have been reported. However, the interaction between OSA and pain-related temporomandibular disorder (TMD) remains obscure. METHODS: A total of 60 adults (male/female, 48/12; mean age, 41.7 ± 13.2 years) with pain-related TMD were enrolled. All participants underwent overnight full-channel polysomnography and had assessment of size and position of the tongue, tonsillar size, height, and weight. Diagnostic Criteria/TMD criteria was applied to diagnose TMD. Myofascial trigger points (TrPs) were bilaterally evaluated in the two masticatory and four cervical muscles including the temporalis, masseter, trapezius, sternocleidomastoid, occipitalis, and splenius capitis muscles. Participants were divided into three groups in accordance with their levels of OSA. RESULTS: The significantly higher number of active TrPs were detected in participants with severe OSA. The number of active TrPs in the masticatory muscles significantly interacted with diverse types of apneic and arousal indices. CONCLUSION: The myofascial pain modulating mechanisms and jaw function could have interactions with nocturnal hypoxia and sleep fragmentation in chronic pain-related TMD patients.

Influences of decision preferences and health literacy on temporomandibular disorder treatment outcome.

BACKGROUND: Shared decision-making is defined as the process by which physicians and informed patients make a shared medical decision, taking into account the preferences and values of the patients. It is well known that shared decision-making practices improve both clinicians' and patients' satisfaction and lead to better treatment outcomes. The aim of the study was to assess associations between patients' roles in decision-making, health literacy levels, and treatment outcomes of temporomandibular disorders (TMDs). METHODS: In total, 131 participants were enrolled. Participants underwent interview and physical examination at baseline and six months after TMD management. TMD was diagnosed according to Diagnostic Criteria/TMD criteria. Myofascial trigger points were bilaterally evaluated in the two masticatory muscles including the temporalis and masseter muscles. The roles that participants preferred to play or had perceived during decision-making and their health literacy levels were assessed using Control Preferences Scale and Newest Vital Sign, respectively. RESULTS: Participants who perceived themselves as occupying active roles in decision-making showed higher health literacy levels than those with passive perceived roles. Participants with appropriate health literacy showed higher perceived participation levels in decision-making than did those with limited health literacy. The extent of subjective symptomatic improvement after six months of treatment showed significant associations with perceived role in decision-making, despite lack of significant relationships between perceived role in decision-making and the extent of improvement of objective parameters. CONCLUSION: Active participation of patients in decision-making improves the satisfaction but limited health literacy constitutes barriers to effective patient engagement during TMD management.

Relationship between skeletal bone mineral density and subjective masticatory difficulty.

BACKGROUND: Masticatory ability is an essential factor for sustaining quality of life and social and systemic well-being, particularly in elderly. This study aimed to reveal the association between subjective masticatory difficulty and skeletal bone mineral density (BMD). METHODS: Data from the Korean National Health and Nutrition Examination Survey, which was conducted from 2008 to 2011 were analyzed. This study included 13,092 Koreans (5656 males, 7436 females) over 50 years of age. Masticatory difficulty was evaluated based on a self-reported questionnaire. Areal BMD of the total hip, femoral neck, and lumbar spine as well as lean body mass were determined using dual-energy X-ray absorptiometry. Data about the sociodemographic characteristics, physical activity, number of teeth present, sum of decayed, missing, and filled permanent teeth (DMFT) index and Community Periodontal Index (CPI) were collected. Multivariate logistic regression analysis was conducted to analyze associations between subjective masticatory difficulty and BMD, adjusting for the confounding covariates. RESULTS: Significant differences were observed in the areal BMD of the total hip, femoral neck, and lumbar spine as well as lean body mass accordance with the presence of subjective masticatory difficulty in both males and females. The number of teeth, DMFT, and CPI score did not show significant differences based on the presence of self-reported satisfaction of chewing performance in both males and females. Results from multivariate logistic regression demonstrated that the subjective masticatory difficulty showed significant interactions with skeletal BMD and the associations between masticatory satisfaction and BMD of the total hip and femoral neck were more prominent in females compared to those in males. CONCLUSIONS: The skeletal BMD, particularly areal BMD of the femoral neck was significantly associated with subjective masticatory difficulty in elderly, especially in elder females.

Coordination of the leucine-sensing Rag GTPase cycle by leucyl-tRNA synthetase in the mTORC1 signaling pathway.

A protein synthesis enzyme, leucyl-tRNA synthetase (LRS), serves as a leucine sensor for the mechanistic target of rapamycin complex 1 (mTORC1), which is a central effector for protein synthesis, metabolism, autophagy, and cell growth. However, its significance in mTORC1 signaling and cancer growth and its functional relationship with other suggested leucine signal mediators are not well-understood. Here we show the kinetics of the Rag GTPase cycle during leucine signaling and that LRS serves as an initiating "ON" switch via GTP hydrolysis of RagD that drives the entire Rag GTPase cycle, whereas Sestrin2 functions as an "OFF" switch by controlling GTP hydrolysis of RagB in the Rag GTPase-mTORC1 axis. The LRS-RagD axis showed a positive correlation with mTORC1 activity in cancer tissues and cells. The GTP-GDP cycle of the RagD-RagB pair, rather than the RagC-RagA pair, is critical for leucine-induced mTORC1 activation. The active RagD-RagB pair can overcome the absence of the RagC-RagA pair, but the opposite is not the case. This work suggests that the GTPase cycle of RagD-RagB coordinated by LRS and Sestrin2 is critical for controlling mTORC1 activation, and thus will extend the current understanding of the amino acid-sensing mechanism.

Bone mineral density, bone microstructure, and bone turnover markers in females with temporomandibular joint osteoarthritis.

OBJECTIVE: The pathogenesis of the temporomandibular joint osteoarthritis (TMJ OA) has not been clearly revealed. This study aimed to investigate the pathogenesis of TMJ OA based on bone metabolism. METHODS: Fifty-nine young (mean age 23.4 ± 3.4 years) and 41 post-menopausal females (mean age 57.2 ± 4.6 years) were enrolled. Areal bone mineral density (aBMD) was measured via dual-energy X-ray absorptiometry of the lumbar spine, femoral neck, total hip, and ultradistal radius. Levels of four bone resorption markers, serum ionized calcium and C-telopeptide of type I collagen (CTx) and urinary N-telopeptide of type I collagen and deoxypyridinoline, two bone formation markers, serum bone alkaline phosphatase and osteocalcin, and serum 25-dihydroxyvitamin D were analyzed at baseline and after 12 months. Condylar bone quality was assessed by 3D reconstructed CT images. RESULTS: Significant differences in condylar bone quality and aBMDs of the lumbar spine in accordance with TMJ OA stages were observed in young and post-menopausal females. The level of CTx was significantly associated with the development and progression of TMJ OA only in young females, whereas 25-dihydroxyvitamine D demonstrated significant associations in young and post-menopausal females. Progression of TMJ OA was accompanied by reduced condylar bone quality and concomitant with lower lumbar spine aBMDs in young and post-menopausal females. CONCLUSION: Bone metabolism and condylar quality might be involved in the development and progression of TMJ OA. CLINICAL RELEVANCE: CTx could be considered as a potential diagnostic and monitoring marker in young females, and vitamin D showed a therapeutic potential for TMJ OA.

Neck associated factors related to migraine in adolescents with painful temporomandibular disorders.

OBJECTIVE: Migraine is a comorbidity of painful temporomandibular disorders (TMDs). Both migraine and painful TMD have associations with neck pain and head posture. The aim of this study was to clarify the role of neck pain and head posture on the association between migraine and painful TMD in adolescents. MATERIALS AND METHOD: In total 314 adolescents were included: 235 adolescents with only painful TMD (pTMD) and 79 adolescents with painful TMD and migraine (TMDMIG). Adolescents were diagnosed according to the Research Diagnostic Criteria for Temporomandibular Disorders and International Classification of Headache Disorders, 3rd edition. Head postures were identified using lateral cephalograms. Myofascial trigger points (TrPs) were evaluated in the temporalis, masseter, trapezius, sternocleidomastoid, sub-occipitalis, and splenius capitis muscles. RESULTS: Multivariate logistic regression analysis confirmed the associations among the orofacial pain duration, number of active TrPs in the trapezius muscles, intensity of neck pain, and distance between the occiput and atlas and migraine in adolescents with TMD. The relationships among intensity of neck pain, number of TrPs in the cervical muscles, and head posture were more prominent in the TMDMIG than those in the pTMD. CONCLUSION: Neck associated factors seemed to have relevance with migraine in adolescents with painful TMD.

Associations Among Temporomandibular Joint Osteoarthritis, Airway Dimensions, and Head and Neck Posture.

PURPOSE: This study sought to investigate associations among progressive temporomandibular joint osteoarthritis (TMJ OA), airway dimensions, and head and neck posture. MATERIALS AND METHODS: In total, 114 temporomandibular disorders (TMDs) patients were enrolled. Among 114 patients, 28 had no pathologic bony changes in the TMJ condyles (TMDnoOA), 45 had progressive TMJ OA (TMJOApro), and 41 demonstrated TMJ OA which had not progressed for 12 months (TMJOAnopro). TMJ OA was diagnosed based on the Diagnostic Criteria for TMD axis I. Computed tomography (CT) images and lateral cephalograms were obtained at baseline (T0) and 12 months after treatment (T1). The head and neck posture and airway area in upright position were analyzed using lateral cephalograms whereas airway volume in supine position was determined by 3D reconstructed CT images. RESULTS: The volume change of the oropharynx in supine position was more prominent in the TMJOApro than in the TMDnoOA but no significant differences in changes in the pharyngeal airway while in upright position were detected. The retrognathic facial profile became more remarkable at T1 in the TMJOApro and TMJOAnopro compared to those at T0. The forward head posture seemed to be progressed in the TMJOApro than in either the TMJOAnopro or TMDnoOA. CONCLUSION: Progressive TMJ OA may have associations with retrognathia and decreased oropharyngeal airway volume in the supine position but not in the upright position. Progressive TMJ OA may be related with altered head posture in the upright position to compensate for reduced airway dimensions.

Development of an Oral and Maxillofacial Frailty Index: A preliminary study.

OBJECTIVE: The purpose of this study is to develop an index to measure oral and maxillofacial frailty in older adults as an acceptable screening tool. METHODS: Three hundred adults (aged ≥ 50 years) participated in this study by telephone interview. Ten candidate items for the Oral and Maxillofacial Frailty Index (OMFI) and 20 matched detailed items for oral and maxillofacial functions were asked. Information about sociodemographic and oral health-related variables was also obtained. The test-retest reliability of the 10 candidate items was determined. Correlations of the 10 candidate items with the 20 detailed items or sociodemographic and oral health-related variables were analysed to test the validity of the candidate items. To suggest optimal items for the OMFI, five different models with different numbers of items were constructed and evaluated based on their associations with main variables. RESULTS: The overall internal consistency of the 10 candidate items was .704, and the Cronbach's alpha value of each item was .23-.55. The test-retest reliability was excellent. There were significant correlations between the 10 candidate and 20 matched detailed items. The score of the 10 candidate items was significantly different according to gender, education level and oral health-related variables. The final five items for the OMFI were difficulties in chewing, the necessity of water when eating dry food, difficulties in jaw or tongue movements, difficulties in speaking or pronunciation and difficulties in facial expression. CONCLUSIONS: The five items could be used as a screening tool for evaluating oral and maxillofacial frailty in older adults.

Blood contamination in salivary diagnostics: current methods and their limitations.

The use of saliva samples in clinical studies has increased. However, the diagnostic value of whole saliva is compromised in the presence of blood contamination, owing to the higher levels of analytes in blood compared with those in saliva. The aim of this study was to review the existing methods and their limitations for measuring the levels of blood contamination in saliva. A literature search was performed using Web of Science, SCOPUS, and PubMed databases and 49 articles dealing with salivary diagnostics and measurements of blood contamination were included. Five methods for measuring the degree of blood components in saliva were discussed, including "visual inspection", use of "strip for urinalysis", and detection of plasma proteins such as "hemoglobin", "albumin", and "transferrin". Each method has its limitations, and transferrin has been regarded as the most reliable and valid marker for blood contamination in saliva. However, transferrin in whole saliva may not be solely a product of blood, and its level in whole saliva can be influenced by several factors such as age, gonadal hormones, salivary flow rate, chewing performance, and oral microorganisms. In conclusion, when quantitatively analyzing whole saliva samples, the influence of blood contamination should be considered.

Skeletal maturation and predicted adult height in adolescents with temporomandibular joint osteoarthritis.

BACKGROUND: The occurrence of osteoarthritis (OA) of the temporomandibular joint (TMJ) in juveniles could be associated with fluctuating levels of oestrogen and growth hormone (GH) during adolescence. OBJECTIVE: To investigate extent of skeletal maturation and predicted adult height in adolescents with TMJ OA. METHOD: In total, 155 adolescents (54 males, 101 females; mean age, 14.1 ± 2.0 years) were enrolled. Among them, 19 adolescents (CON) showed no sign of TMD, 50 adolescents exhibited signs of disc displacement but did not have TMJ OA (TMDnoOA), 23 adolescents exhibited the initial stage of TMJ OA (TMJOAini) and 63 adolescents exhibited the severe stage of TMJ OA (TMJOApro). TMJ OA was diagnosed based on the Research Diagnostic Criteria axis I and bone age was estimated using the Greulich-Pyle method. The height, weight and body mass index of participated adolescents were measured and statistically converted to z-scores. The predicted adult height and age of peak height velocity (APHV) were calculated using the BoneXpert® software. RESULTS: In female adolescents, the differences between the chronological and bone ages were significantly higher and the z-score for height was significantly lower in the TMJOApro. Female adolescents with TMJOA exhibited a significantly shorter predicted adult height and earlier APHV than those in the CON and TMDnoOA. CONCLUSION: The adolescents with TMJ OA exhibited premature skeletal maturations and short predicted adult stature, particularly the female adolescents.

Clinical factors affecting salivary transferrin level, a marker of blood contamination in salivary analysis.

BACKGROUND: Diagnostic value of whole saliva may be compromised when blood contamination is present in saliva samples. Measuring transferrin level in saliva samples has been used for detecting the level of blood contamination in saliva. The aim of this study was to investigate the validity of transferrin as a proper biomarker for blood contamination in whole saliva. METHODS: Thirty younger (mean age: 25.9 ± 2.1 years) and twenty older (mean age: 65.1 ± 9.0 years) females were included. The index reflecting overall gingival inflammation (total gingival index), salivary flow rate, and salivary concentration and secretion rate of transferrin of each subject were analyzed. RESULTS: Salivary transferrin concentrations and secretion rates were higher in the younger females than in the older ones despite a lower total gingival index in the younger females. The total gingival index showed no significant correlations with the concentration or secretion rate of transferrin in either unstimulated or stimulated whole saliva of younger and older subjects. The salivary concentration of transferrin showed negative correlations with the flow rate of saliva in both the younger and older groups. There were significant positive correlations between the salivary concentrations and secretion rates of transferrin in both the younger and older groups. CONCLUSIONS: Salivary transferrin levels could be affected by other factors as well as the level of blood contamination. The influences of age, gonadal hormones, salivary flow rate, and chewing performance need to be considered when using the salivary level of transferrin as a blood contamination marker.