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.

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.

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.

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.

Patient-reported change of sensibility and pain after parotid and labial gland biopsy applied for primary Sjögren's syndrome diagnostics: one-year follow-up study.

OBJECTIVES: To assess how patients perceived pain and change of sensibility of the biopsied area after having undergone parotid and labial gland biopsy as part of the diagnostic work-up of primary Sjögren's syndrome (pSS). METHODS: Simultaneously, parotid and labial salivary gland biopsies were taken under local anesthesia. One week, 6 months and 12 months post-operatively, each patient was sent a postal questionnaire to quantify the severity of pain and change of sensibility in the biopsied areas with a visual analogue scale (VAS; range 0-100). RESULTS: 110 patients were included. The median age of patients was 54 years (IQR=47-65) and 92% were female. Changes in sensibility and pain in the biopsied area were significantly higher after a parotid gland biopsy than after a labial gland biopsy at one week and 6 months post-operatively, but rather minor in both areas. At 12 months post-operatively, the change in sensibility and pain level was negligible in most patients and comparable for both biopsied areas. The duration of the technique, outcome of the biopsy, exposure of nerve branches during the biopsy and bleeding during the biopsy did not affect the reported change of sensibility or pain in the biopsied area. ESSPRI was not related to pain level or change of sensibility at any time point (r<0.3 and p>0.05). CONCLUSIONS: Patient-reported post-operative change of sensibility and pain in the area of the parotid and labial gland biopsy are minor and comparable. Parotid and labial gland biopsies are diagnostic techniques well tolerated by patients suspected with pSS.

Patients with advanced periodontal disease before intensity-modulated radiation therapy are prone to develop bone healing problems: a 2-year prospective follow-up study.

PURPOSE: Intensity-modulated radiation therapy (IMRT) has changed radiation treatment of head and neck cancer (HNC). However, it is still unclear if and how IMRT changes oral morbidity outcomes. In this prospective study, we assessed the outcome of reducing post-IMRT sequelae by means of pre-radiation dental screening and eliminating oral foci. METHODS: All consecutive dentate patients > 18 years, diagnosed with primary oral or oropharyngeal carcinoma, referred for pre-treatment dental screening between May 2011 and May 2013, were included and followed for 2 years. Patients were treated with IMRT or IMRT with chemotherapy (CHIMRT). Dental screening data, demographic data, and data on oral sequelae during follow-up were recorded. Diagnosed oral foci were treated before start of the radiation therapy. RESULTS: Oral foci were found in 44/56 (79%) patients, consisting predominantly of periodontal breakdown. Bone healing problems after radiotherapy occurred more often in patients with periodontal pockets ≥ 6 mm at baseline (19 vs. 4% in patients with pockets < 6 mm). Osteoradionecrosis developed in 4/56 patients (7%) during follow-up. In line with this observation, multiple logistic regression analysis showed that the periodontal inflamed surface area, which is higher in patients with more severe periodontal disease, predicted that a patient has a higher risk on developing osteoradionecrosis or bone healing problems (p = 0.028). CONCLUSIONS: Patients with severe periodontal disease before IMRT/CHIMRT are more prone to develop bone healing problems post-radiotherapy.

Ultrasound of the Major Salivary Glands is a Reliable Imaging Technique in Patients with Clinically Suspected Primary Sjögren's Syndrome.

OBJECTIVE: To assess the inter- and intraobserver reliability of ultrasound of major salivary glands in patients clinically suspected of having primary Sjögren's syndrome (pSS) as well as to assess sources of variation in outcomes of ultrasonographic evaluation. METHODS: 80 consecutive outpatients with clinically suspected pSS underwent ultrasound evaluation. The following ultrasound variables of the parotid and submandibular salivary glands were assessed: echogenicity, parenchymal homogeneity, presence of hypoechogenic areas, hyperechogenic reflections and clearness of posterior glandular border, according to the scoring system of Hocevar et al. (total score range: 0 - 48). Images were scored independently by three blinded observers in two sessions. RESULTS: The intraobserver reliability of the total ultrasound score was excellent, with an intraclass correlation (ICC) ranging from 0.89 to 0.96. The interobserver reliability was good to excellent, with ICCs of 0.84 and 0.76 for the total ultrasound score in the two sessions. The kappa value ranged from 0.60 to 0.83 depending on the applied cut-offs (cut-off score ≥ 15 and ≥ 17). Hypoechogenic areas and homogeneity of parotid glands showed the highest interobserver reliability. The median kappa for echogenicity was low. The total ultrasound scores varied more between observers in patients with higher ultrasonographic scores (approximately scores ≥ 20). CONCLUSION: Ultrasound of major salivary glands is a reliable imaging technique for patients with clinically suspected pSS. Discrepancies between observers in assessing the severity of ultrasound findings may interfere with detecting 'true' changes over time. When monitoring the progression of pSS or treatment efficacy, it is advised that a particular patient be scored by the same ultrasonographer at every time point.

Physical fatigue characterises patient experience of primary Sjögren's syndrome.

OBJECTIVES: Besides ocular and oral dryness, fatigue is a major symptom in patients with primary Sjögren's syndrome (pSS). Our aim was to investigate the importance of fatigue in relation to other symptoms experienced as well as to evaluate the effect of rituximab treatment on fatigue in pSS patients with active disease. METHODS: This analysis was based on data from our open-label rituximab study in 28 pSS patients. Symptoms of dryness, physical fatigue, pain, and mental fatigue were scored on 0-10 scales (according to ESSPRI). Systemic disease activity was assessed with ESSDAI. RESULTS: At baseline, 24 (86%) patients rated physical fatigue as the complaint most eligible for improvement (median importance of 10), followed by pain, dryness, and mental fatigue. After rituximab treatment, physical fatigue showed maximum improvement of 2.5 points and 31% in median values at group level, and 10 (36%) patients reached physical fatigue score<5 representing patient-acceptable symptom state (PASS). In comparison, systemic disease activity improved 5.5 points and 73% at group level, and 22 (79%) patients reached ESSDAI<5 representing low disease activity. GEE analysis over time revealed that physical fatigue was significantly associated with absolute number of B cells, dryness and mental fatigue, but not with ESSDAI, IgG levels and IgM-RF. CONCLUSIONS: Physical fatigue characterises patient experience of pSS. Rituximab treatment resulted in significant improvement of patient-reported symptoms. However, the large majority of patients still experienced physical fatigue at an unsatisfactory level, above the cut-off value for PASS. Therefore, attention for optimal management of this prominent symptom is warranted.

Ig gene analysis reveals altered selective pressures on Ig-producing cells in parotid glands of primary Sjögren's syndrome patients.

In this study, we sought to understand the selective pressures shaping the Ig-producing cell repertoire in the parotid glands of primary Sjögren's syndrome (pSS) patients before and after rituximab treatment (RTX). In particular, we evaluated the role of potential N-glycosylation motifs acquired by somatic hypermutation (ac-Nglycs) within Ig H chain V region (IGHV) genes as alternative selective pressures for B cells in pSS. Five pSS patients received RTX. Sequential parotid salivary gland biopsies were taken before RTX, at 12 wk and at 36-52 wk after treatment. Parotid biopsies from four non-pSS patients served as controls. Sequence analysis was carried out on the IgA and IgG RNA transcripts expressing IGHV3 genes in all parotid biopsies. Both IgG and IgA sequences from pSS patients exhibited no evidence for positive Ag-driven selection pressure in their CDRs in contrast to non-pSS controls. The prevalence of IgG sequences with ac-Nglycs was significantly higher in pSS patients than in non-pSS controls. Selection pressures shaping the IgG and IgA repertoire within pSS patients' parotid glands are distinct from those in non-pSS controls, with very little evidence for positive (auto)antigen selection. The higher prevalence of ac-Nglycs on pSS-IgG compared with non-pSS IgG indicates that ac-Nglycs could be an alternative form of selection pressure. We speculate that B cell hyperproliferation within parotid glands of pSS patients may result from Ag-independent interactions such as that between glycosylated B cell receptors and lectins within the microenvironment rather than (auto)antigen-specific stimulation. Our study brings a new perspective into research on pSS.

Towards personalised treatment in primary Sjögren's syndrome: baseline parotid histopathology predicts responsiveness to rituximab treatment.

OBJECTIVES: The aims of this study were (1) to assess the effect of rituximab (RTX; anti-CD20) treatment in patients with primary Sjögren's syndrome (pSS) based on sequential parotid biopsies obtained in a placebo-controlled, randomised clinical trial, and (2) to assess the prognostic value of the histological characteristics of parotid gland tissue with regard to responsiveness to RTX treatment. METHODS: In a double-blinded, placebo-controlled trial, sequential parotid gland biopsies were taken from 20 RTX-treated and 10 placebo-treated patients with pSS, at baseline and 12 weeks after treatment. The relative amount of lymphocytic infiltrate (stained for CD45), absolute number of T cells and B cells per mm2 parenchyma (stained for CD3 and CD20, respectively), focus score, number of germinal centres and of lymphoepithelial lesions per mm2 in parotid gland parenchyma were assessed. Histopathological data were compared between clinical responders (decrease in European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (ESSDAI) score of ≥3 at 12 weeks compared with baseline) and non-responders (change in ESSDAI<3) to RTX treatment. RESULTS: In RTX-treated patients, a significant reduction in the number of CD20+ B cells/mm2 parenchyma was observed, while no such reduction was observed in placebo-treated patients. The number of CD3+ T cells/mm2 in parenchyma did not change in either group. Furthermore, the number and the severity of lymphoepithelial lesions/mm2 and number of germinal centres/mm2 was significantly reduced in RTX-treated patients, but did not change in placebo-treated patients. When comparing the pretreatment characteristics of clinical responders with non-responders, the median number of CD20+ B cells/mm2 parenchyma at baseline was significantly higher in responders (1871 vs 353 cells/mm2, p<0.05). Other histopathological baseline characteristics were not predictive for response to RTX treatment. CONCLUSIONS: RTX treatment in pSS leads to a major reduction of lymphocytic infiltration and to fewer B cells, germinal centres and lymphoepithelial lesions in parotid gland parenchyma. A high pretreatment number of CD20+ B cells/mm2 parotid gland parenchyma predicts better responsiveness of patients with pSS to RTX treatment. Pretreatment parotid gland histopathological characteristics could therefore contribute to a more personalised treatment approach to pSS.

Connecting salivary gland inflammation to specific symptoms in Sjögren's disease.

INTRODUCTION: The complex nature of Sjögren's Disease (SjD) necessitates a comprehensive and patient-centered approach in both diagnosis and management. This narrative review emphasizes the need for a holistic understanding of the connection between salivary gland inflammation and oral symptoms in SjD. AREAS COVERED: The intricate relationship between salivary gland inflammation and dry mouth is explored, highlighting the variability in associations reported in studies. The association of the severity of xerostomia and degree of inflammation is also discussed. The frequent presence of recurrent sialadenitis in SjD further accentuates the connection of compromised salivary gland function and inflammation. The review additionally discusses local inflammatory factors assessed through salivary gland biopsies, which could potentially serve as predictors for lymphoma development in SjD. Insights into compromised quality of life and hypercoagulable state and their association with salivary gland inflammations are provided. Advancements in noninvasive imaging techniques, particularly salivary gland ultrasonography and color Doppler ultrasound, offer promising avenues for noninvasive assessment of inflammation. EXPERT OPINION: There is a need for longitudinal studies to unravel the connections between salivary gland inflammation and oral symptoms. This will enhance management strategies and optimize treatment outcomes for SjD patients.

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 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.

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 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.

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.