Can ultrasound of the major salivary glands differentiate Sjögren's disease from its major mimics?

OBJECTIVES: Ultrasound of the major salivary glands (SGUS) is widely used to assess the major salivary glands in Sjögren's disease (SjD). Little is known, however, regarding the diagnostic accuracy of SGUS to differentiate SjD from its mimics. This study aims to investigate the diagnostic accuracy of SGUS in differentiating SjD from other diseases with salivary gland involvement. METHODS: SGUS was performed in 20 consecutive patients with SjD and 20 consecutive patients with well-established systemic disease, i.e., with either sarcoidosis, amyloidosis, HIV infection or chronic HCV infection. Images were scored independently by two blinded observers using the Hocevar scoring system. Diagnostic accuracy to discriminate between the patient (sub-)groups was explored. RESULTS: The accuracy of SGUS to differentiate SjD from other systemic diseases was excellent (area under ROC curve of 0.91). The optimal cut-off value to define positive or negative ultrasound for SS was 15. Sensitivity, specificity, positive predictive value and negative predictive value were high, varying from 85-90%, and diagnostic odds ratio was 51. SGUS was positive in the vast majority of SjD patients (n=18), but also in 2 patients with HIV infection and one patient with sarcoidosis. SGUS score differed significantly between patients with SjD and other systemic diseases (median 27 vs. 10, p<0.001) as well as between SjD patients and patients with either sarcoidosis, amyloidosis, HIV or HCV infection (all p<0.05). CONCLUSIONS: This study indicates that SGUS has a potentially high diagnostic accuracy to discriminate SjD from systemic diseases which can also cause salivary gland involvement.

Immune markers and microbial factors are related with periodontitis severity in people with HIV.

OBJECTIVE: The objective of the study is to assess systemic immune markers and microbial factors related to periodontitis severity in people living with HIV. METHODS: Eighty people living with HIV (PLWH), who exhibited in the last two viral load measurements < 40 copies/mL, underwent full-mouth periodontal examinations and sub-gingival plaque sampling. Periodontitis was classified according to the CDC-AAP case definition. Inflammation, immune-activation, and immunosenescence markers were assessed, microbiological analyses were performed, and oral care routines and HIV characteristics were noted. RESULTS: From our group of PLWH, 42.5% and 57.5% suffered from moderate and severe periodontitis, respectively. Oral care habits did not differ between PLWH with moderate and severe periodontitis. Bacterial subgingival plaque loads were higher, and Porphyromonas gingivalis was more prevalent in PLWH with severe periodontitis than with moderate periodontitis (53% vs 7%, respectively). Mean C-reactive protein levels [CRP, 1.6 mg/L versus 0.8 mg/L, p = 0.020] and percentages of senescent CD28-CD57 + CD8 + T-cells in peripheral blood [16.5 versus 8.9, p = 0.035] were higher with severe periodontitis. Infection duration, CD4 count, CD4/CD8 ratio and type of antiretroviral therapy did not differ between both groups. CONCLUSIONS: Periodontitis severity is related to increased prevalence of Porphyromonas gingivalis, elevated CRP levels, and higher frequencies of circulating CD8 + senescent cells in PLWH.

Can salivary gland ultrasonography replace salivary gland biopsy in the diagnosis of Sjögren's syndrome?

Ultrasound is a promising diagnostic method when it comes to assessing the involvement of major salivary glands in patients with primary Sjögren's syndrome (pSS). A matter of debate is whether ultrasound of the major salivary glands (SGUS) can replace a salivary gland biopsy in the diagnosis or classification of pSS. The intra- and inter-observer reliability of SGUS was found to be good, especially when focusing on hypoechogenic areas and homogeneity, and comparable to the reliability of histopathologic characteristics of salivary gland biopsies of pSS patients. However, replacing salivary gland biopsy by SGUS led to substantial decrease of the accuracy of the 2016 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria with clinical diagnosis as the gold standard. When SGUS was added as an additional item to the criteria, the accuracy of the criteria remained high, offering at the same time the clinicians a wider array of tools to assess patients. Combination of SGUS and anti-SSA antibodies was shown to be highly predictive of the classification of a patient suspected of pSS, making routine salivary gland biopsy debatable.

Four-Dimensional Determination of the Patient-Specific Centre of Rotation for Total Temporomandibular Joint Replacements: Following the Groningen Principle.

For patients who suffer from severe dysfunction of the temporomandibular joint (TMJ), a total joint replacement (TJR) in the form of a prosthesis may be indicated. The position of the centre of rotation in TJRs is crucial for good postoperative oral function; however, it is not determined patient-specifically (PS) in any current TMJ-TJR. The aim of this current study was to develop a 4D-workflow to ascertain the PS mean axis of rotation, or fixed hinge, that mimics the patient's specific physiological mouth opening. Twenty healthy adult patients were asked to volunteer for a 4D-scanning procedure. From these 4D-scanning recordings of mouth opening exercises, patient-specific centres of rotation and axes of rotation were determined using our JawAnalyser tool. The mean CR location was positioned 28 [mm] inferiorly and 5.5 [mm] posteriorly to the centre of condyle (CoC). The 95% confidence interval ranged from 22.9 to 33.7 [mm] inferior and 3.1 to 7.8 [mm] posterior to the CoC. This study succeeded in developing an accurate 4D-workflow to determine a PS mean axis of rotation that mimics the patient's specific physiological mouth opening. Furthermore, a change in concept is necessary for all commercially available TMJ-TJR prostheses in order to comply with the PS CRs calculated by our study. In the meantime, it seems wise to stick to placing the CR 15 [mm] inferiorly to the CoC, or even beyond, towards 28 [mm] if the patient's anatomy allows this.

A Contemporary Approach to Non-Invasive 3D Determination of Individual Masticatory Muscle Forces: A Proof of Concept.

Over the past decade, the demand for three-dimensional (3D) patient-specific (PS) modelling and simulations has increased considerably; they are now widely available and generally accepted as part of patient care. However, the patient specificity of current PS designs is often limited to this patient-matched fit and lacks individual mechanical aspects, or parameters, that conform to the specific patient's needs in terms of biomechanical acceptance. Most biomechanical models of the mandible, e.g., finite element analyses (FEA), often used to design reconstructive implants or total joint replacement devices for the temporomandibular joint (TMJ), make use of a literature-based (mean) simplified muscular model of the masticatory muscles. A muscle's cross-section seems proportionally related to its maximum contractile force and can be multiplied by an intrinsic strength constant, which previously has been calculated to be a constant of 37 [N/cm2]. Here, we propose a contemporary method to determine the patient-specific intrinsic strength value of the elevator mouth-closing muscles. The hypothesis is that patient-specific individual mandible elevator muscle forces can be approximated in a non-invasive manner. MRI muscle delineation was combined with bite force measurements and 3D-FEA to determine PS intrinsic strength values. The subject-specific intrinsic strength values were 40.6 [N/cm2] and 25.6 [N/cm2] for the 29- and 56-year-old subjects, respectively. Despite using a small cohort in this proof of concept study, we show that there is great variation between our subjects' individual muscular intrinsic strength. This variation, together with the difference between our individual results and those presented in the literature, emphasises the value of our patient-specific muscle modelling and intrinsic strength determination protocol to ensure accurate biomechanical analyses and simulations. Furthermore, it suggests that average muscular models may only be sufficiently accurate for biomechanical analyses at a macro-scale level. A future larger cohort study will put the patient-specific intrinsic strength values in perspective.

Reproducibility of 2D and 3D Ramus Height Measurements in Facial Asymmetry.

In our clinic, the current preferred primary treatment regime for unilateral condylar hyperactivity is a proportional condylectomy in order to prevent secondary orthognathic surgery. Until recently, to determine the indicated size of reduction during surgery, we used a 'panorex-free-hand' method to measure the difference between left and right ramus heights. The problem encountered with this method was that our TMJ surgeons measured differences in the amount to resect during surgery. Other 2D and 3D method comparisons were unavailable. The aim of this study was to determine the most reproducible ramus height measuring method. Differences in left/right ramus height were measured in 32 patients using three methods: one 3D and two 2D. The inter- and intra-observer reliabilities were determined for each method. All methods showed excellent intra-observer reliability (ICC > 0.9). Excellent inter-observer reliability was also attained with the panorex-bisection method (ICC > 0.9), while the CBCT and panorex-free-hand gave good results (0.75 < ICC < 0.9). However, the lower boundary of the 95% CI (0.06−0.97) of the inter-observer reliability regarding the panorex-free-hand was poor. Therefore, we discourage the use of the panorex-free-hand method to measure ramus height differences in clinical practice. The panorex-bisection method was the most reproducible method. When planning a proportional condylectomy, we advise applying the panorex-bisection method or using an optimized 3D-measuring method.

Volumetric Effect and Patient Satisfaction after Facial Fat Grafting.

BACKGROUND: Facial fat grafts decrease in volume after transplantation. This observation is based on overall facial three-dimensional analyses, because there is sparse information on volume changes in well-defined aesthetic areas. The authors aimed to assess the overall and, more specifically, the local volumetric effects of facial fat grafting and relate these effects to patient satisfaction up to 1 year after treatment. METHODS: All consecutive adult female patients who were scheduled for facial fat grafting without additional surgical procedures were asked to participate. All patients underwent the same fat grafting method. An algorithm-based personalized aesthetic template was applied to define specific aesthetic areas on the preoperative three-dimensional image. Objective outcome parameters [i.e., three-dimensional volume differences, patient satisfaction (FACE-Q questionnaire)] were measured at baseline and at 6 weeks, 6 months, and 12 months after fat grafting. RESULTS: Of 33 female patients who underwent a facial fat graft procedure, 23 patients had complete three-dimensional data and were eligible for analysis. The highest volume gain was observed 6 weeks after grafting and was followed by a gradual loss thereafter. Overall and in the zygomatic area, a substantial gain in volume was still present 1 year after grafting, whereas this effect was lost in the lip area. FACE-Q scales Satisfaction with Facial Appearance Overall and Satisfaction with Cheeks improved too, whereas scores for Lines: Lips returned to baseline levels. The improvement in FACE-Q scales was in agreement with the objective change in volume. CONCLUSION: Gain in overall and local volumetric effects is accompanied by comparable changes in patient satisfaction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

A clinical decision aid for patients with suspected midfacial and mandibular fractures (the REDUCTION-I study): a prospective multicentre cohort study.

PURPOSE: To assess physical examination findings related to maxillofacial trauma to identify patients at risk of midfacial and mandibular fractures and then to construct a clinical decision aid to rule out the presence of midfacial and mandibular fractures in emergency department patients. METHODS: We performed a prospective multicentre cohort study in four hospitals in the Netherlands, including consecutive patients with maxillofacial trauma. Each patient received a standardized physical examination consisting of 15 and 14 findings for midfacial and mandibular traumas, respectively. Consequently, clinical decision aids were constructed with the focus being on ruling out the presence of midfacial and mandibular fractures, and diagnostic accuracy was calculated. RESULTS: A total of 993 consecutive patients were identified of whom 766 and 280 patients were suspected of midfacial and mandibular fractures, respectively. Midfacial fractures were diagnosed in 339 patients (44.3%), whereas mandibular fractures were observed in 66 patients (23.6%). The decision aid for midfacial trauma consisting of peri-orbital hematoma, epistaxis, ocular movement limitation, infra-orbital nerve paresthesia, palpable step-off and tooth mobility or avulsion, produced a sensitivity of 89.7 (86.0-92.5), a specificity of 42.6 (38.0-47.4), and a negative predictive value of 83.9% (78.4-88.2). The decision aid for mandibular trauma consisting of the angular compression test, axial chin pressure test, objective malocclusion, tooth mobility or avulsion and the tongue blade bite test resulted in a sensitivity of 98.5 (91.9-99.7), a specificity of 34.6 (28.5-41.2), and a negative predictive value of 98.7% (92.8-99.8). CONCLUSION: The constructed clinical decision aids for maxillofacial trauma may aid in stratifying patients suspected for midfacial and mandibular fractures to reduce unnecessary diagnostic imaging. CLINICAL TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov with the identifier NCT03314480.

Diagnostic accuracy of physical examination findings for midfacial fractures: a systematic review and meta-analysis.

OBJECTIVES: To conduct a systematic review and meta-analysis to assess the diagnostic accuracy of physical examination findings and related clinical decision aids for midfacial fractures in comparison to computed tomography and cone beam computed tomography. MATERIAL AND METHODS: A systematic review was performed by searching the MEDLINE, Cochrane, EMBASE, and CINAHL databases. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Pooled sensitivity, specificity, and diagnostic odds ratios with the corresponding 95% confidence intervals were calculated for each physical examination finding and reported clinical decision aids. RESULTS: After screening 2367 records, 12 studies were included. High risk of patient selection bias was detected in three studies (25%). Additionally, high concerns regarding applicability were found for the patient selection in five studies (41.7%), and for the reference standard in eleven studies (91.7%). Of the total 42 individual physical examination findings, only 31 were suitable for a meta-analysis. High specificity and low sensitivity were found for most findings. The pooled diagnostic odds ratio ranged from 1.07 to 11.38. Clinical decision aids were reported by 8 studies, but none were constructed specifically for midfacial fractures. CONCLUSION: Based on the current available evidence, the absence of physical examination findings can successfully identify patients who do not have a midfacial fracture, but the presence of individual findings does not necessarily mean that the patient has a midfacial fracture. Although various clinical decision aids were presented, none focused on exclusively midfacial fractures. CLINICAL RELEVANCE: The diagnostic accuracy of physical examination findings can be used to diagnose a midfacial fracture so as to reduce unnecessary imaging, health care costs, and exposure to ionizing radiation.

A clinical decision aid to discern patients without and with midfacial and mandibular fractures that require treatment (the REDUCTION-II study): a prospective multicentre cohort study.

PURPOSE: To assess the diagnostic accuracy of physical examination findings and to construct clinical decision aids to discern emergency department patients without and with midfacial and mandibular fractures that require treatment. METHODS: A prospective multicentre cohort study was conducted in four hospitals in the Netherlands. Consecutive maxillofacial trauma patients were included whereupon each patient underwent a standardized physical examination consisting of 15 and 14 findings for midfacial and mandibular trauma, respectively. The primary outcome was the decision whether to treat during the emergency department stay or within 24 h of admission. The diagnostic accuracy was calculated for the individual physical examination findings and ensuing clinical decision aids with the focus being on detecting midfacial and mandibular fractures that require active treatment. RESULTS: A total of 766 midfacial trauma patients were identified of whom 339 (44.3%) had midfacial fractures. Of those, 74 (21.8%) required active treatment. A total of 280 mandibular trauma patients were identified of whom 66 (23.6%) had mandibular fractures. Of those, 37 (56.0%) required active treatment. The decision aid for midfacial trauma consisting of facial depression, epistaxis, ocular movement limitation, palpable step-off, objective malocclusion and tooth mobility or avulsion had a sensitivity of 97.3 (90.7-99.3), a specificity of 38.6 (35.0-42.3), and a negative predictive value of 99.3 (97.3-99.8). The decision aid for mandibular trauma consisting of mouth opening limitation, jaw movement pain, objective malocclusion and tooth mobility or avulsion resulted in a sensitivity of 100.0 (90.6-100.0), a specificity of 39.1 (33.2-45.4), and a negative predictive value of 100.0 (96.1-100.0). CONCLUSION: The clinical decision aids successfully identified midfacial and mandibular trauma patients requiring active fracture treatment and so may be useful in preventing unnecessary radiological procedures in the future. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov with the identifier NCT03314480.

Low Mutational Burden of Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue in Patients with Primary Sjogren's Syndrome.

Patients with primary Sjogren's syndrome (pSS) are at risk of developing extranodal marginal zone lymphoma (ENMZL) of the mucosa-associated lymphoid tissue (MALT) in the parotid glands. Unlike recurrent genomic aberrations observed in MALT lymphoma, which were not associated with pSS (non-pSS), it is unknown which somatic aberrations underlie the development of pSS-associated MALT lymphomas. Whole-exome sequencing was performed on 17 pSS-associated MALT lymphomas. In total, 222 nonsynonymous somatic variants affecting 182 genes were identified across the 17 cases. The median number of variants was seven (range 2-78), including three cases with a relatively high mutational load (≥24/case). Out of 16 recurrently mutated genes, ID3, TBL1XR1, PAX5, IGLL5 and APC are known to be associated with lymphomagenesis. A total of 18 copy number alterations were detected in eight cases. MALT1 translocations were not detected. With respect to outcome, only two cases relapsed outside of the salivary glands. Both had a high mutational load, suggesting a more advanced stage of lymphoma. The low mutational load and lack of a clear lymphoma-related mutation profile suggests that localized pSS-associated MALT lymphomas are genomically more stable than non-pSS MALT lymphomas and most likely depend on a stimulatory micro-environment.

The ESTMJS (European Society of Temporomandibular Joint Surgeons) Consensus and Evidence-Based Recommendations on Management of Condylar Dislocation.

Although condylar dislocation is not uncommon, terminology, diagnostics, and treatment concepts vary considerably worldwide. This study aims to present a consensus recommendation based on systematically reviewed literature and approved by the European Society of TMJ Surgeons (ESTMJS). Based on the template of the evidence-based German guideline (register # 007-063) the ESTMJS members voted on 30 draft recommendations regarding terminology, diagnostics, and treatment initially via a blinded modified Delphi procedure. After unblinding, a discussion and voting followed, using a structured consensus process in 2019. An independent moderator documented and evaluated voting results and alterations from the original draft. Although the results of the preliminary voting were very heterogenous and differed significantly from the German S3 guideline (p < 0.0005), a strong consensus was achieved in the final voting on terminology, diagnostics, and treatment. In this voting, multiple alterations, including adding and discarding recommendations, led to 24 final recommendations on assessment and management of TMJ dislocation. To our knowledge, the ESTMJS condylar dislocation recommendations are the first both evidence and consensus-based international recommendations in the field of TMJ surgery. We recommend they form the basis for clinical practice guidelines for the management of dislocations of the mandibular condyle.

Parotid salivary sodium levels of Sjögren's syndrome patients suggest B-cell mediated epithelial sodium channel disruption.

Patients with primary Sjögren's syndrome (SS) suffer widely from lack of saliva production. Here we investigate potential mechanisms underpinning changes in SS patient saliva composition. Sodium concentration was significantly higher in all saliva samples collected: unstimulated submandibular/sublingual (SmSl) saliva (p<0.0001), stimulated SmSl saliva (p=0.002) and stimulated parotid (PG) (p<0.0001) saliva, compared to non-SS sicca controls. Chloride, phosphate and potassium ion concentrations, α-amylase activity and total protein content correlations were less consistently changed between SS and non-SS saliva types. Stimulated PG salivary sodium levels correlated with the degree of CD45+ lymphocytic cell infiltrate in the parotid glands (r=0.69, p<0.001), and even more strongly so with infiltrating CD20+ B cells (r=0.73, p<0.0001). CD3+ T cells were only moderately correlated with salivary sodium (r=0.23, p=0.015). In non-SS control or focus score (FS) negative SS PG tissue, the epithelial sodium channel (ENaC), responsible for sodium transport out of saliva, was localised to the apical membrane of luminal striated duct cells. In PG tissue from FS+ SS patients, apical ENaC expression appeared absent. We hypothesise that B cell-related proinflammatory cytokines in SS salivary glands may dysregulate sodium transport channels in SS.

The Transcriptome of Paired Major and Minor Salivary Gland Tissue in Patients With Primary Sjögren's Syndrome.

Background: While all salivary glands (SGs) can be involved in primary Sjögren's syndrome (pSS), their respective role in pathogenesis remains unclear. Our objective was to assess immunopathway activation in paired parotid and labial gland tissue from biopsy-positive and biopsy-negative pSS and non-SS sicca patients. Methods: Paraffin-embedded, paired parotid and labial salivary gland tissue and peripheral blood mononuclear cells were obtained from 39 pSS and 20 non-SS sicca patients. RNA was extracted, complementary DNA libraries were prepared and sequenced. For analysis of differentially expressed genes (DEGs), patients were subdivided based on fulfillment of ACR-EULAR criteria and histopathology. Results: With principal component analysis, only biopsy-positive pSS could be separated from non-SS sicca patients based on SG gene expression. When comparing the transcriptome of biopsy-positive pSS and biopsy-negative non-SS sicca patients, 1235 and 624 DEGs (FDR<0.05, log2FC<-1 or >1) were identified for parotid and labial glands, respectively. The number of DEGs between biopsy-negative pSS and non-SS sicca patients was scarce. Overall, transcript expression levels correlated strongly between parotid and labial glands (R2 = 0.86, p-value<0.0001). Gene signatures present in both glands of biopsy-positive pSS patients included IFN-α signaling, IL-12/IL-18 signaling, CD3/CD28 T-cell activation, CD40 signaling in B-cells, DN2 B-cells, and FcRL4+ B-cells. Signature scores varied considerably amongst pSS patients. Conclusion: Transcriptomes of paired major and minor SGs in pSS were overall comparable, although significant inter-individual heterogeneity in immunopathway activation existed. The SG transcriptome of biopsy-negative pSS was indistinguishable from non-SS sicca patients. Different patterns of SG immunopathway activation in pSS argue for personalized treatment approaches.

Diagnostic accuracy of physical examination findings for midfacial and mandibular fractures.

OBJECTIVES: To assess the diagnostic accuracy of physical examination findings used to identify patients at risk for midfacial or mandibular fractures. MATERIALS AND METHODS: A five-year retrospective cohort was constructed from all emergency department patients with a midfacial or mandibular trauma. The sensitivity, specificity, pre-test probability, positive predictive value, negative predictive value, positive likelihood ratio and negative likelihood ratio data was calculated for 19 and 14 physical examination findings for midfacial and mandibular fractures respectively. Computed Tomography and panoramic radiography were used as index tests. RESULTS: A total of 1484 patients were identified among whom 40.4% midfacial and 33.4% mandibular fractures were diagnosed. Overall, specificity was found to be higher than sensitivity. Regarding midfacial fractures, high specificity was found for raccoon eyes, malar eminence flattening and all the findings that are related to palpation, the nasal, ocular and intra-oral assessment. Malar eminence flattening, external nasal deformity, nasal septum hematoma, change of globe position and palpable step-off had ad high positive predictive value and positive likelihood ratio. Regarding mandibular fractures high specificity was found for mouth opening restriction, auditory canal bleeding, intra-oral assessment related findings, palpable step-off, inferior alveolar nerve paresthesia, the angular compression test and chin axial pressure test. CONCLUSIONS: The diagnostic accuracy of relevant physical examination findings were identified for the prediction of midfacial and mandibular fractures.

Gene expression profiling of epithelium-associated FcRL4+ B cells in primary Sjögren's syndrome reveals a pathogenic signature.

In primary Sjögren's syndrome (pSS), FcRL4+ B cells are present in inflamed salivary gland tissue, within or in close proximity to ductal epithelium. FcRL4 is also expressed by nearly all pSS-related mucosa-associated lymphoid tissue (MALT) B cell lymphomas, linking FcRL4 expression to lymphomagenesis. Whether glandular FcRL4+ B cells are pathogenic, how these cells originate, and how they functionally differ from FcRL4- B cells in pSS is unclear. This study aimed to investigate the phenotype and function of FcRL4+ B cells in the periphery and parotid gland tissue of patients with pSS. First, circulating FcRL4+ B cells from 44 pSS and 54 non-SS-sicca patients were analyzed by flow cytometry. Additionally, RNA sequencing of FcRL4+ B cells sorted from parotid gland cell suspensions of 6 pSS patients was performed. B cells were sorted from cell suspensions as mini bulk (5 cells/well) based on the following definitions: CD19+CD27-FcRL4- ('naive'), CD19+CD27+FcRL4- ('memory'), and CD19+FcRL4+ B cells. We found that, although FcRL4+ B cells were not enriched in blood in pSS compared with non-SS sicca patients, these cells generally exhibited a pro-inflammatory phenotype. Genes coding for CD11c (ITGAX), T-bet (TBX21), TACI (TNFRSF13B), Src tyrosine kinases and NF-κB pathway-related genes were, among others, significantly upregulated in glandular FcRL4+ B cells versus FcRL4- B cells. Pathway analysis showed upregulation of B cell activation, cell cycle and metabolic pathways. Thus, FcRL4+ B cells in pSS exhibit many characteristics of chronically activated, pro-inflammatory B cells and their gene expression profile suggests increased risk of lymphomagenesis. We postulate that these cells contribute significantly to the epithelial damage seen in the glandular tissue and that FcRL4+ B cells are an important treatment target in pSS.

Research Frontiers in Oral Toxicities of Cancer Therapies: Osteoradionecrosis of the Jaws.

The deleterious effects of head and neck radiation on bone, with osteoradionecrosis (ORN) as the major disabling side effect of head and neck cancer treatment, are difficult to prevent and hard to treat. This review focuses on the current state of the science regarding the pathobiology, clinical impact, and management of ORN. With regard to the pathobiology underlying ORN, it is not yet confirmed whether the current radiation schedules by 3-dimensional conformal radiotherapy and intensity modified radiotherapy result in an unchanged, decreased, or increased risk of developing ORN when compared with conventional radiation treatment, the main risk factor being the total radiation dose delivered on any clinically significant surface of the mandible. With regard to the prevention of ORN, a thorough, early pre-irradiation dental assessment is still considered the first step to reduce the hazard of developing ORN post-radiotherapy, and hyperbaric oxygen (HBO) treatment reduces the risk of developing ORN in case of dental surgery in an irradiated field. With regard to the treatment of ORN, the focus is bidirectional: elimination of the necrotic bone and improving the vascularity of the normal tissues that were included in the radiation portal. The cure rate of limited ORN by conservative therapy is approximately 50%, and the cure rate of surgical approaches when conservative therapy has failed is approximately 40%. Whether it is effective to support conservative or surgical treatment with HBO as an adjuvant is not set. HBO treatment is shown to increase the vascularity of hard and soft tissues and has been reported to be beneficial in selected cases. However, in randomized clinical trials comparing the preventive effect of HBO on developing ORN with, eg, antibiotic coverage in patients needing dental surgery, the preventive effect of HBO was not shown to surpass that of a more conservative approach. More recently, pharmacologic management was introduced in the treatment of ORN with success, but its efficacy has to be confirmed in randomized clinical trials. The major problem of performing well-designed randomized clinical trials in ORN is having access to large numbers of patients with well-defined, comparable cases of ORN. Because many institutions will not have large numbers of such ORN cases, national and international scientific societies must be approached to join multicenter trials. Fortunately, the interest of funding organizations and the number researchers with an interest in healthy aging is growing. Research aimed at prevention and reduction of the morbidity of cancer treatment fits well within these programs.

Concurrent validity and reliability of cephalometric analysis using smartphone apps and computer software.

OBJECTIVES: To assess the diagnostic accuracy of two smartphone cephalometric analysis apps compared with Viewbox software. MATERIALS AND METHODS: Pretreatment digital lateral cephalograms of 50 consecutive orthodontic patients (20 males, 30 females; mean age, 19.1 years; SD, 11.7) were traced twice using two apps (ie, CephNinja and OneCeph), with Viewbox used as the gold standard computer software program. Seven angular and two linear measurements, originally derived from Steiner cephalometric analysis, were performed. RESULTS: Regarding validity, intraclass correlation coefficients (ICCs) ranged from .903-.983 and .786-.978 for OneCeph vs Viewbox and CephNinja vs Viewbox, respectively. The ICC values for intratool reliability ranged from .647-.993. None of the CephNinja measurements was below the recommended cutoff values of ICCs for reliability. CONCLUSIONS: OneCeph has a high validity compared with Viewbox, while CephNinja is the best alternative to Viewbox regarding reliability. Smartphone apps may have a great potential in supplementing traditional cephalometric analysis.