A novel discriminant algorithm for differential diagnosis of mild to moderate thalassemia and iron deficiency anemia.

BACKGROUND: Mild to moderate thalassemia trait (TT) and iron deficiency anemia (IDA) are the most common conditions of microcytic hypochromic anemia (MHA) and they exhibit highly similar clinical and laboratory features. It is sometimes difficult to make a differential diagnosis between TT and IDA in clinical practice. Therefore, a simple, effective, and reliable index is needed to discriminate between TT and IDA. METHODS: Data of 598 patients (320 for TT and 278 for IDA) were enrolled and randomly assigned to training set (278 of 598, 70%) and validation set (320 of 598, 30%). Stepwise discriminant analysis was used to define the best diagnostic formula for the discrimination between TT and IDA in training set. The accuracy and diagnostic performance of formula was tested and verified by receiver operating characteristic (ROC) analysis in validation set and its diagnostic performance was compared with other published indices. RESULTS: A novel formula, Thalassemia and IDA Discrimination Index (TIDI) = -13.932 + 0.434 × RBC + 0.033 × Hb + 0.025 ×MCHC + 53.593 × RET%, was developed to discriminate TT from IDA. TIDI showed a high discrimination performance in ROC analysis, with the Area Under the Curve (AUC) = 0.936, Youden' s index = 78.7%, sensitivity = 89.5%, specificity = 89.2%, respectively. Furthermore, the formula index also obtained a good classification performance in distinguishing 5 common genotypes of TT from IDA (AUC from 0.854-0.987). CONCLUSION: The new, simple algorithm can be used as an effective and robust tool for the differential diagnosis of mild to moderate TT and IDA in Guangxi region, China.

CsSPL13A directly binds and positively regulates CsFT and CsBAM to accelerate flowering in cucumber.

Flowering is an important developmental transition that greatly affects the yield of many vegetable crops. In cucumber (Cucumis sativus), flowering is regulated by various factors including squamosa promoter-binding-like (SPL) family proteins. However, the role of CsSPL genes in cucumber flowering remains largely unknown. In this study, we cloned the squamosa promoter-binding-like protein 13A (CsSPL13A) gene, which encodes a highly conserved SBP-domain protein that acts as a transcription factor and localizes to the nucleus. Quantitative real-time PCR (qRT-PCR) analysis showed that CsSPL13A was mainly expressed in flowers, and its expression level increased significantly nearing the flowering stage. Additionally, compared with the wild type(WT), CsSPL13A-overexpressing transgenic cucumber plants (CsSPL13A-OE) showed considerable differences in flowering phenotypes, such as early flowering, increased number of male flowers, and longer flower stalks. CsSPL13A upregulated the expression of the flowering integrator gene Flowering Locus T (CsFT) and the sugar-mediated flowering gene ß-amylase (CsBAM) in cucumber. Yeast one-hybrid and firefly enzyme reporter assays confirmed that the CsSPL13A protein could directly bind to the promoters of CsFT and CsBAM, suggesting that CsSPL13A works together with CsFT and CsBAM to mediate flowering in cucumber. Overall, our results provide novel insights into the regulatory network of flowering in cucumber as well as new ideas for the genetic improvement of cucumber varieties.

Development of a tool for monitoring the jaw-opening pace and preliminary comparison the pace between young and old ages.

OBJECTIVES: Studies have demonstrated that high-speed jaw-opening exercises are effective in improving swallowing function. However, there has been no objective tool available for monitoring jaw-opening pace. This study aimed to develop an objective tool for monitoring and validating jaw-opening pace and compare it between young and old ages from different age groups. MATERIALS AND METHODS: A load cell plug-in jaw pad connected to an automatic recording and analysis system was used to record jaw-opening motions for offline analysis. We recruited 58 healthy volunteers from different age groups (20-39 y/o; 40-59y/o; 60-79y/o). During a 2-min recording session, each participant was instructed to fully open and close their jaw as quickly as possible while wearing a sensor. Bland-Altman plot, paired t-test and Pearson's correlation test were used to compare the number of jaw-opening motions between manual counting and automatic software analysis. The number of jaw-opening motions during the 2-min recording was compared between the three age groups. RESULTS: Automated analysis of jaw-opening pace was efficient and equally comparable with the traditional manual counting method across the three age groups. A declining trend in jaw-opening pace among the old age group was found but with no statistically significant difference. CONCLUSIONS: A jaw-opening motion monitoring tool with reliable automatic pace analysis software was validated in young and old ages. The jaw-opening pace demonstrated a tendency to decline with age. CLINICAL RELEVANCE: This monitoring tool can also be used to provide visual feedback during jaw-opening motion training in pace control.

Age-Dependent Association Between Body Mass Index and All-Cause Mortality Among Patients with Hypertension: A Longitudinal Population-Based Cohort Study in China.

Purpose: The association between body mass index (BMI) and all-cause mortality may vary among hypertensive patients of different ages. This study aimed to investigate the age-dependent association between BMI and all-cause mortality among patients with hypertension. Patients and Methods: A total of 212,394 participants with hypertension aged 20-85 years from Minhang Hypertension Standardization Management System in Shanghai of China were included. Follow-up began at the time when individuals were first recorded and ended at death, loss to follow-up, or December 31, 2018, whichever came first. Additive Cox proportional hazards models with thin plate smoothing functions and conventional Cox proportional hazards models were adopted to examine the relationship between BMI, age, and mortality. The joint effect of BMI and age on mortality was assessed using a bivariate response model. Results: We found that the BMI-mortality relationship followed a U-shaped pattern, with a trough at 26-27 kg/m2. Compared with normal weight, underweight was associated with a 50% increased risk of premature mortality (hazard ratio 1.50, 95% confidence interval 1.43 to 1.57). Whereas among those aged 45-59 and 60-85 years, overweight was associated with 13% (0.87, 0.80 to 0.94) and 18% (0.82, 0.80 to 0.84) reduction in risk of death, respectively. Bivariate response model indicated a significant interaction between BMI and age (P < 0.05). Among younger and older patients, we found a descending trend for mortality risk, with BMI increasing at different age levels, whereas a reverse J-shaped relation pattern was observed among middle-aged patients. Conclusion: The impact of BMI on all-cause mortality in hypertensive patients varies with age, and moderate weight gain may benefit longevity in middle-aged and older patients.

MiR-630 Promotes Radioresistance by Induction of Anti-Apoptotic Effect via Nrf2-GPX2 Molecular Axis in Head-Neck Cancer.

Head and neck cancer (HNC) ranks among the top ten prevalent cancers worldwide. Radiotherapy stands as a pivotal treatment component for HNC; however, radioresistance in cancerous cells often leads to local recurrence, becoming a substantial factor in treatment failure. MicroRNAs (miRNAs) are compact, non-coding RNAs that regulate gene expression by targeting mRNAs to inhibit protein translation. Although several studies have indicated that the dysregulation of miRNAs is intricately linked with malignant transformation, understanding this molecular family's role in radioresistance remains limited. This study determined the role of miR-630 in regulating radiosensitivity in HNC. We discovered that miR-630 functions as an oncomiR, marked by its overexpression in HNC patients, correlating with a poorer prognosis. We further delineated the malignant function of miR-630 in HNC cells. While it had a minimal impact on cell growth, the miR-630 contributed to radioresistance in HNC cells. This result was supported by decreased cellular apoptosis and caspase enzyme activities. Moreover, miR-630 overexpression mitigated irradiation-induced DNA damage, evidenced by the reduced levels of the γ-H2AX histone protein, a marker for double-strand DNA breaks. Mechanistically, the overexpression of miR-630 decreased the cellular ROS levels and initiated Nrf2 transcriptional activity, resulting in the upregulation of the antioxidant enzyme GPX2. Thus, this study elucidates that miR-630 augments radioresistance by inducing an anti-apoptotic effect via the Nrf2-GPX2 molecular axis in HNC. The modulation of miR-630 may serve as a novel radiosensitizing target for HNC.

Lip and tongue strength associated with chewing patterns in aging population.

BACKGROUND: Improving chewing function of older adults increases the health-related quality of life. Few studies indicated the correlation between tongue, lip strength on masticatory performance in older people. The study aimed to investigate the association between lip, tongue strength on chewing pattern in aging population. METHODS: The older adults had independent daily intake without assistance were enrolled. They had intact dentition and no periodontitis. To estimate the number of chewing strokes and chewing time by consuming a cornstarch cookie were used to represent chewing pattern. Lip and tongue pressure were evaluated with an Iowa Oral Performance Instrument. Linear regression analysis was used to analyze the lip and tongue pressure associated with the chewing time and strokes. Spearman's correlation analysis was utilized to evaluate the associations among chewing time and chewing strokes or lip and tongue pressure. RESULTS: 35 women and 35 men with an average age of 73.2 years were investigated. Tongue pressure was significantly related to the chewing time and the number of chewing strokes (p = 0.01 and 0.03). There was a close association between chewing time and the number of chewing strokes (p < 0.0001). The correlation between lip and tongue pressure was significant (p < 0.0001). CONCLUSION: The tongue strength significantly related to chewing ability in aging population. Increasing the tongue strength greatly reduced the number of chewing strokes and chewing time. Good masticatory ability could increase the motor function of tongue; raising the tongue strength might be able to improve mastication in older adults.

Third-generation sequencing for genetic disease.

Third-generation sequencing (TGS) has led to a brave new revolution in detecting genetic diseases over the last few years. TGS has been rapidly developed for genetic disease applications owing to its significant advantages such as long read length, rapid detection, and precise detection of complex and rare structural variants. This approach greatly improves the efficiency of disease diagnosis and complements the shortcomings of short-read sequencing. In this paper, we first briefly introduce the working mechanism of one of the most important representatives of TGS, single-molecule real-time (SMRT) sequencing by Pacific Bioscience (PacBio), followed by a review and comparison of the advantages and disadvantages of different sequencing technologies. Finally, we focused on the progress of SMRT sequencing applications in genetic disease detection. Future perspectives on the applications of TGS in other fields were also presented. With the continuous innovation of the SMRT technologies and the expansion of their fields of application, SMRT sequencing has broad clinical application prospects in genetic diseases detection, and is expected to become an important tool for the molecular diagnosis of other diseases.

Non-syndromic enlarged vestibular aqueduct caused by novel compound mutations of the SLC26A4 gene: a case report and literature review.

Enlarged vestibular aqueduct is an autosomal genetic disease mainly caused by mutations in the SLC26A4 gene and includes non-syndromic and syndromic types. This study aimed to identify genetic defects in a Chinese patient with non-syndromic enlarged vestibular aqueduct (NSEVA) and to investigate the impact of variants on the severity of non-syndromic enlarged vestibular aqueduct. A male patient with NSEVA, aged approximately 6 years, was recruited for this study. The clinical characteristics and results of auxiliary examinations, including laboratory and imaging examinations, were collected, and 127 common hereditary deafness genes were detected by chip capture high-throughput sequencing. Protein structure predictions, the potential impact of mutations, and multiple sequence alignments were analyzed in silico. Compound heterozygote mutations c.1523_1528delinsAC (p.Thr508Asnfs*3) and c.422T>C (p.Phe141Ser) in the SLC26A4 gene were identified. The novel frameshift mutation c.1523_1528delinsAC produces a severely truncated pendrin protein, and c.422T>C has been suggested to be a disease-causing mutation. Therefore, this study demonstrates that the novel mutation c.1523_1528delinsAC in compound heterozygosity with c.422T>C in the SLC26A4 gene is likely to be the cause of NSEVA. Cochlear implants are the preferred treatment modality for patients with NSEVA and severe-to-profound sensorineural hearing loss Genetic counseling and prenatal diagnosis are essential for early diagnosis. These findings expand the mutational spectrum of SLC26A4 and improve our understanding of the molecular mechanisms underlying NSEVA.

Cbx7 promotes the generation of induced pluripotent stem cells.

The iPS cells were discovered in 2006. With their ability to differentiate into cells of all three germ layers, iPS cells have great potential for clinical applications. Oct4, Sox2, c-Myc, and Klf4 were identified as the most effective factors for generating iPS cells. Despite this, iPS cells manufactured with these factors would still be inefficient. As a member of the chromobox family, chromobox protein homolog 7 (Cbx7) binds to PRC1 and PRC2 to inhibit genes involved in differentiation. A decrease in the expression of Cbx7 is observed during embryonic stem cell differentiation. Currently, no report discusses the role of Cbx7 in the production of iPS cells. In this study, we hypothesized that Cbx7 could increase iPS cell generation. We confirmed that Cbx7 is highly expressed in pluripotent stem cells (including ES and iPS cells). In addition, transfecting Cbx7 into fibroblasts increased Oct4, Sox2, c-Myc, and Klf4 expression. Moreover, we describe a novel approach to producing iPS cells using Cbx7 in combination with Oct4, Sox2, c-Myc, and Klf4. In summary, we have demonstrated that Cbx7 enhances the reprogramming of iPS cells and characterized the stemness and pluripotency of iPS cells.

Surface Electromyography for Evaluating the Effect of Aging on the Coordination of Swallowing Muscles.

Swallowing function can deteriorate with age, leading to a risk of dysphagia. Swallowing evaluation by surface electromyography (sEMG) can be easily and extensively applied for an elderly population. This study evaluated the temporal events observed by sEMG to clarify how aging affects the coordination among the masticatory and suprahyoid muscles. We recruited elderly individuals (over 65 years old) who denied dysphagia. The sEMG activities of anterior temporalis, masseter, and suprahyoid muscles were recorded during 3, 15, and 30 ml water swallowing tests (WST). We calculated the time interval between anterior temporalis and suprahyoid peak activity (T-SH interval) and masseter and suprahyoid peak activity (M-SH interval) and analyzed their correlation with age. The subjects who could and could not swallow 30 ml of water in one gulp were further assigned into the one-gulp and piecemeal groups, respectively, for subgroup analysis. We recruited 101 subjects, among whom 75 (26 males and 49 females) were analyzed after excluding those with suspected dysphagia or low-quality sEMG recordings. Age was significantly correlated with the bilateral T-SH (left: r = 0.249, p = 0.031; right: r = 0.412, p < 0.01) and right M-SH (r = 0.242, p = 0.037) intervals in the 30 ml WST. The correlation between intervals and age were observed in both subgroups. sEMG can be used to investigate the effect of aging on the temporal coordination between masticatory and suprahyoid contraction. Further studies are needed to verify the validity of screening subclinical dysphagia in the elderly.

Identification and characterization of extrachromosomal circular DNA in patients with high myopia and cataract.

To explore the presence of extrachromosomal circular DNA (eccDNA) in the anterior capsule of the lens in the eyes of patients with cataract and with high myopia. Circle-Seq was performed to identify differences in the eccDNA and gene expression between the anterior capsule of the lens of patients with simple nuclear cataract (C, n = 6 cases) and patients with nuclear cataract along with high myopia (HM, n = 6 cases). The expression of eccDNA was confirmed using routine quantitative polymerase chain reaction. The eccDNA ranked in C and HM ranged in length from 0.017 kb - 9.9 Mb with two distinctive peaks detected at 0.2 kb and 0.5 kb, while eccDNA that were differentially expressed ranged in size from 0.05 kb - 57.8 kb with two distinctive peaks observed at 0.1 kb and 0.5 kb. Only 2.5% of the eccDNA in C and 2% in HM were>25 kb in size. The gene-rich chromosomes contributed to more number of eccDNA/Mb, while several well-known high myopia candidate genes, including catenin delta 2 (CTNND2) and ubiquitin-like with PHD, exhibited significantly increased levels of eccDNA in the anterior capsule of the lens in patients with high myopia. This study highlighted the topologic analysis of the anterior capsule of eyes with high myopia, which is an emerging direction for research and clinical applications. These findings suggested that eccDNA was commonly detected in eyes with high myopia and cataracts, and the candidate genes for high myopia identified in previous studies were also observed in the eccDNA.

Ph-Positive B-Cell Acute Lymphoblastic Leukemia Occurring after Receipt of Bivalent SARS-CoV-2 mRNA Vaccine Booster: A Case Report.

The coronavirus disease 2019 (COVID-19) pandemic is a universal emergency public health issue. A large proportion of the world's population has had several spike antigen exposures to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and/or COVID-19 vaccinations in a relatively short-term period. Although sporadic hematopoietic adverse events after COVID-19 vaccine inoculation were reported, there is currently no sufficient evidence correlating anti-spike protein immune responses and hematopoietic adverse events of vaccinations. We reported the first case of Ph-positive B-cell acute lymphoblastic leukemia (ALL) occurring after a bivalent mRNA COVID-19 vaccine inoculation. The otherwise healthy 43-year-old female patient had a total of six spike antigen exposures in the past 1.5 years. Informative pre-vaccine tests and bone marrow study results were provided. Although the causal relationship between bivalent vaccinations and the subsequent development of Ph-positive B-cell ALL cannot be determined in the case report, we propose that anti-spike protein immune responses could be a trigger for leukemia. Clinicians must investigate the hematopoietic adverse events closely after COVID-19 vaccinations. Further pre-clinical studies to investigate the safety of bivalent mRNA COVID-19 vaccine are required.

A Blood-Responsive AIE Bioprobe for the Ultrasensitive Detection and Assessment of Subarachnoid Hemorrhage.

Subarachnoid hemorrhage (SAH) is a severe subtype of stroke caused by the rupturing of blood vessels in the brain. The ability to accurately assess the degree of bleeding in an SAH model is crucial for understanding the brain-damage mechanisms and developing therapeutic strategies. However, current methods are unable to monitor microbleeding owing to their limited sensitivities. Herein, a new bleeding assessment system using a bioprobe TTVP with aggregation-induced emission (AIE) characteristics is demonstrated. TTVP is a water-soluble, small-molecule probe that specifically interacts with blood. Taking advantage of its AIE characteristics, cell membranes affinity, and albumin-targeting ability, TTVP fluoresces in bleeding areas and detects the presence of blood with a high signal-to-noise (S/N) ratio. The degree of SAH bleeding in an endovascular perforation model is clearly evaluated based on the intensity of the fluorescence observed in the brain, which enables the ultrasensitive detection of mirco-bleeding in the SAH model in a manner that outperforms the current imaging strategies. This method serves as a promising tool for the sensitive analysis of the degree of bleeding in SAHs and other hemorrhagic diseases.

Convergent angles of a tapered implant referred from the root profile of premolars.

Background/purpose: Limited studies have discussed the convergent profiles regarding tapered implants based on biological considerations. This study analyzed the convergent angles (CAs) of premolar roots and imitated a tapered implant according to the anatomy of tooth roots. Materials and methods: A total of 60 single-rooted premolars were explored by micro-computed tomography. Every individual root was divided into 10 segments corono-apically, and the roots' buccolingual (BL) and mesiodistal (MD) CAs were measured by sections. To mimic a dental implant, the irregular shape of examined root cross-sections was transformed into a circular shape with equal areas. A biomimetic dental implant (BDI) was reconstructed and its CAs were compared with those of the natural roots' BL and MD at the examined levels and overall estimation. Results: In general, the maxillary and mandibular premolars demonstrated comparable CA patterns. However, significantly different CA patterns of BL, MD, and BDI were developed for both the maxillary and mandibular roots at the examined levels. The BL's CAs were greater than those CAs measured from the BDI and MD aspects, particularly for the sections at the middle and apical thirds of the roots. For overall CAs, the BDI's CAs were comparable with the average CAs of the BL and MD for both premolar groups. Conclusion: Instead of a cylindrical configuration, the BDI prototype demonstrated a tapered model with a continuous slope. The average CA of BDI was 14°-24°, serving as a biological reference for future tapered implant design and research.

Tumor Suppressor miRNA-503 Inhibits Cell Invasion in Head and Neck Cancer through the Wnt Signaling Pathway via the WNT3A/MMP Molecular Axis.

Head and neck cancer (HNC) is the fifth most common cancer worldwide, and its incidence and death rates have been consistently high throughout the past decades. MicroRNAs (miRNAs) have recently gained significant attention because of their role in the regulation of a variety of biological processes via post-transcriptional silencing mechanisms. Previously, we determined a specific profile of miRNAs associated with HNC using a miRNA microarray analysis. Of the 23 miRNAs with highly altered expression in HNC cells, miR-503 was the most significantly downregulated miRNA. In this study, we confirmed that miR-503 acts as a tumor suppressor, as our results showed decreased levels of miR-503 in cancer cells and patients with HNC. We further characterized the role of miR-503 in the malignant functions of HNC. Although there was a minimal effect on cell growth, miR-503 was found to inhibit cellular invasion significantly. Algorithm-based studies identified multiple potential target genes and pathways associated with oncogenic mechanisms. The candidate target gene, WNT3A, was confirmed to be downregulated by miR-503 at both the mRNA and protein levels and validated by a reporter assay. Furthermore, miR-503 modulated multiple invasion-associated genes, including matrix metalloproteinases (MMPs), through the Wnt downstream signaling pathway. Overall, this study demonstrates that miR-503 suppresses HNC malignancy by inhibiting cell invasion through the Wnt signaling pathway via the WNT3A/MMP molecular axis. The modulation of miR-503 may be a novel therapeutic approach to intervene in cancer invasion.

The correlation between two occlusal analyzers for the measurement of bite force.

BACKGROUND: Occlusal force represents masticatory function. Using quantifiable occlusal indicators provides a more objective occlusal force evaluation. In the recent dental practice, digital methods such as the Dental Prescale II (DP2, GC Corp., Tokyo, Japan) and T-scan (T-Scan III v8; Tekscan Inc.) are commonly used in clinics to evaluate treatment outcomes. The T-scan provides the relative bite force (%) compared to the maximal bite force on individual teeth or the unilateral arch. The DP2 can quantify occlusal force, measured in newtons (N), on the half arch or the overall bite, but it is difficult to identify the bite force on an individual tooth. It is difficult to select a device that fulfils all the requirements to record occlusal force. This study aimed to investigate the association between the bite measured by the DPS2 and T-scan to determine whether the measured bite force is comparable through calculation. METHODS: A total of 80 healthy adults, including 41 women and 39 men with a mean age of 38.2, were requested to bite pressure sensitive film sheets ten minutes apart. Linear regression analysis was used to estimate the measured bite force by the DP2 and T-scan. RESULTS: There was a significant positive correlation between the occlusal force measured by the DP2 and T-scan (P < 0.01) when intercept was equal to zero as confounders were adjused. These results provided the comparability of the measured occlusal forces determined by the DP2 and T-scan. CONCLUSION: The estimated bite force determined by DP2 and T-Scan is convertible using the linear equation from this study to increase the value for clinical applications. The estimated bite force from the two quantifiable occlusal indicators are comparable. The two commercially available quantifiable occlusal indicators can be fully adapted to all clinical requirements according to this result.

An enzyme-activatable dual-readout probe for sensitive ß-galactosidase sensing and Escherichia coli analysis.

Rapid and accurate sensing of ß-galactosidase (ß-gal) activity is particularly critical for the early detection of many diseases and has become a topic of interest in recent years. However, most traditional probes for ß-gal sensing often suffer from the disadvantages of narrow dynamic range, low reaction efficiency and are only employed with either colorimetric or fluorescence sensing. Furthermore, ß-galactosidase sensing based assay for efficient detection and antibiotic resistance analysis of Escherichia coli (E.coli) is not available. Here, an enzyme-induced probe assay was reported for dual sensitive fluorescence and colorimetric measurement of ß-gal activity, and was further employed for detection of Escherichia coli and their antibiotic resistance analysis. The DCM-ßgal probe was virtually non-emissive in aqueous solution, while it could be activated by ß-gal to produce bright emission. Under optimized conditions, DCM-ßgal displayed high sensitivity, selectivity and rapid response to ß-gal with a low detection limit of 1.5 × 10-3 U ml-1. Importantly, this assay was successfully applied to sensitive detection of E. coli cells with a fast detection process within 5 h and a low detection concentration of 1 × 103 CFU ml-1. Furthermore, the enzyme-activatable assay was also successfully applied for high throughput E. coli antibiotic resistance analysis. The DCM-ßgal strategy is applied for the first time on the detection of E. coli cells and their antibiotic resistance analysis. It is provided with the advantages of high selectively, a simple operation, low cost and rapid detection. The detection platform can also be extended to analyze the level of ß-gal in other types of cells or biological samples. Overall, the simple, effective and dual-readout assay holds promise for efficient sensing of ß-gal activity and provides a potential tool for E. coli detection and their antibiotic resistance analysis.

The association between the severity of periodontitis and osteonecrosis of the jaw in patients with different cancer locations: a nationwide population-based study.

OBJECTIVES: To determine the relation between the severity of periodontitis and osteonecrosis of the jaw (ONJ) occurrence among different cancer locations and estimate the effect of dental care on ONJ prevention in cancer patients. MATERIALS AND METHODS: This population-based cross-sectional study was conducted through the Longitudinal Health Insurance Database, Taiwan. Patients with malignancies were collected and subdivided into groups according to their different cancer locations, the severity of periodontitis, and dental care. Multivariable logistic regression analysis was performed to assess the associations between ONJ and ONJ-related factors. RESULTS: A total of 8,234 ONJ patients and 32,912 control patients were investigated. Lip, oral cavity, and pharynx malignancies had the highest ONJ risk among all cancer locations (OR from 3.07 to 9.56, P < 0.01). There is a linear relationship between different severities of periodontitis and ONJ. Patients with radiotherapy and severe periodontitis had the highest ONJ risk (adjusted OR, 9.56; 95% CI, 5.34-17.1). Patients with good dental care had a lower ONJ risk. CONCLUSIONS: The periodontal condition and cancer location showed a significant impact on the risk of developing ONJ after adjusting for bisphosphonate use. Good dental care could decrease the risk of ONJ in cancer patients. The severity of periodontitis might be a target to predict the potency of ONJ. CLINICAL RELEVANCE: Dentists must be vigilant about the increased risk of ONJ in cancer patients with periodontitis, especially in the head and neck cancer population. Good dental care is advised for cancer patients with severe periodontitis.

The impact of dental therapy timelines and irradiation dosages on osteoradionecrosis in oral cancer patients: A population-based cohort study.

OBJECTIVES: This study aimed to investigate how different timelines of various dental therapies were related to osteoradionecrosis development under consideration of radiotherapy dosage in patients with oral cancer. MATERIALS AND METHODS: A total of 7,107 oral cancer patients were enrolled, including 88 osteoradionecrosis patients treated with low radiotherapy dosages (<60 Gy) or high radiotherapy dosages (≥60 Gy), from the Longitudinal Health Insurance Database for Catastrophic Illness Patients of Taiwan. Cox proportional hazard regression was used to compare the osteoradionecrosis risk of various dental treatment timelines under different irradiation dosages. RESULTS: In the oral cancer population with low irradiation dosages (<60 Gy), performing periodontal therapy combined with irradiation significantly raised the risk of osteoradionecrosis by 2.21-fold. Starting radiotherapy within three months after dental surgery greatly increased the risk of developing osteoradionecrosis by 1.87-fold. The oral cancer patients treated with high radiation doses (≥60 Gy) receiving dental surgery within one month prior to radiotherapy had a significantly raised osteoradionecrosis occurrence by 1.60-fold. While the dental surgery was performed during the radiotherapy course, the risk of osteoradionecrosis was greatly increased by 2.21-fold. CONCLUSION: For oral cancer patients, performing dental surgery within three months before radiotherapy might significantly induce osteoradionecrosis. Patients that were treated with high irradiation dosages (≥60 Gy) had a higher tendency to develop osteoradionecrosis if they received dental surgery during radiotherapy. Those who were treated with low radiation dosages (<60 Gy) and received periodontal therapy during radiotherapy might have an increased risk in developing osteoradionecrosis.