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Objectives The aim of this study was to assess the histopathological features of the parotid glands in patients with paediatric-onset Sjögren’s disease (pedSjD) in comparison to patients with adult-onset Sjögren’s disease (adSjD).Methods This study was performed in Groningen, the Netherlands. Patients with pedSjD from a diagnostic paediatric cohort (n=19), patients with adSjD from a diagnostic adult cohort (n=32) and patients with adSjD who participated in a clinical trial (n=42) with a baseline parotid gland biopsy were included. Parotid gland biopsies were analysed after (immuno)histological staining for SjD-related histopathological markers and compared between groups.Results All characteristic histopathological features of adSjD were also observed in pedSjD. There were no significant differences in lymphoepithelial lesions or immunoglobulin A (IgA)/IgG plasma cell shift between the pedSjD and the adSjD cohorts. However, compared with the diagnostic adSjD cohort (with comparable total EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI) scores), pedSjD showed more severe lymphocytic infiltration as reflected by a higher focus score (p=0.003), a higher relative surface area of CD45+ infiltrate (p=0.041), higher numbers of B and T lymphocytes/mm2 (p=0.004 and p=0.029, respectively), a higher B/T lymphocyte ratio (p=0.013), higher numbers of CD21+ follicular dendritic cell networks/mm2 (p=0.029) and germinal centres (GC)/mm2 (p=0.002). Compared with the trial adSjD cohort, with significant higher total ESSDAI scores (p=0.001), only the B/T lymphocyte ratio and numbers of GC/mm2 were significantly higher in the pedSjD cohort (p=0.023 and p=0.018, respectively).Conclusion Patients with pedSjD exhibit more pronounced histopathological features compared with patients with adSjD at diagnosis. Notably, the histopathology of patients with pedSjD aligns more closely with that observed in an adSjD clinical trial cohort, with even stronger B lymphocyte involvement.

Abstract Objectives The aim of the systematic review was to compare studies on implant‐supported two‐unit cantilever crowns with two adjacent implant‐supported crowns in the anterior region. The second aim was to assess in a 10‐year prospective comparative pilot study, hard and soft peri‐implant tissue changes in patients with a missing central and adjacent lateral upper incisor, treated with either an implant‐supported two‐unit cantilever crown or two single implant‐supported crowns. Materials and Methods Medline, Embase, and the Cochrane Central Register of Controlled Trials were searched (last search March 1, 2023). Inclusion criteria were studies reporting outcomes of two missing adjacent teeth in the esthetic region and treated with a single implant‐supported two‐unit cantilever fixed dental prosthesis, or with two solitary implant‐supported crowns. Outcome measures assessed included implant survival (primary), changes in marginal bone and gingiva level, restoration survival, subjective and objective esthetic scores, papilla volume, mid‐facial marginal mucosa level, probing depth, bleeding on probing, and biological and technical complications with ≥1‐year follow‐up. In addition, in a 10‐year pilot study, the same outcome measures were assessed of five patients with a single implant‐supported two‐unit cantilever crown and compared with five patients with two adjacent single implant‐supported crowns in the esthetic zone. Results Nine articles with 11 study groups were found eligible for data extraction. Meta‐analyses of implant survival rates were 96.9% (mean follow‐up 3.4 ± 1.4 years) for the implant‐cantilever treatment and 97.6% (mean follow‐up 3.0 ± 1.8 years) for the adjacent implants treatment (p = .79). In the 10‐year comparative pilot study, no clinically relevant changes in hard and soft peri‐implant tissue levels occurred in both groups. Patient satisfaction was also high in both groups. Conclusion Single implant‐supported two‐unit crowns can be a viable alternative to the placement of two adjacent single implant crowns in the esthetic zone.

Oral microorganisms have been found in the cerebral milieu, suggesting the involvement of oral microbiota in the onset and course of Alzheimer’s Disease (AD) through mechanisms such as amyloid-beta accumulation, tau phosphorylation and neuroinflammation. It is still uncertain whether and which oral bacteria are associated with AD. Therefore, the aim of this systematic review was to assess the current evidence for associations between oral microbiota and AD. A database search in Pubmed and Embase resulted in 623 hits. After removing duplicates, 437 papers remained. Of these, 13 papers passed the inclusion criteria and were included for quality/risk of bias assessment and data extraction. Analysis of these 13 studies revealed high heterogeneity in terms of sample size, age, study design and microbiological methods. Quality assessment using the MINORS criteria indicated reasonable to good quality across studies. As a result of the omission of two of the criteria, the quality results may have been biased. There is no conclusive evidence as to if and which oral microbiota are associated with AD since many conflicting results were reported. Although the overall quality of the studies was acceptable, the studies differed in study design and protocol. Further research is needed to clarify this association.

ABSTRACT: Introduction: Scientific literature on COVID-19 has grown rapidly during the pandemic. The aim of this study was to provide a comprehensive overview of the popularity on the web of the available dental publications on COVID-19 and to examine associations amongst article characteristics, online mentions, and citations. Materials and methods: An Altmetric Explorer search was conducted for COVID-19 articles published in dental journals using 3 keywords: COVID-19, SARS-CoV-2, and pandemic. The following Altmetric data were collected: Altmetric attention score (AAS), mentions by news outlets, tweets, Mendeley readers, and Web of Science citations. Additionally, article title, type, topic, origin and open access status, journal title, quartile of impact factor (IF) distribution, and time lapse between COVID-19 pandemic onset and publication date were analysed. Results: In all, 253 articles published in 48 dental journals were eligible for the study. AAS was significantly influenced by article topic, type, origin, and journal IF quartile. There was a negligible correlation between AAS and Web of Science citations. Mendeley was the only Altmetric source highly correlated with citations. Conclusions: There was substantial online interest in COVID-19 dentistry-related literature, as depicted by the AAS of the reviewed articles and social media metrics. Mendeley reader counts were highly correlated with citations, and they may therefore be valuable in research impact evaluation.

Abstract Objectives The aim of the ITI Consensus Workshop on zygomatic implants was to provide Consensus Statements and Clinical Recommendations for the use of zygomatic implants. Materials and methods Three systematic reviews and one narrative review were written to address focused questions on (1) the indications for the use of zygomatic implants; (2) the survival rates and complications associated with surgery in zygomatic implant placement; (3) long-term survival rates of zygomatic implants and (4) the biomechanical principles involved when zygoma implants are placed under functional loads. Based on the reviews, three working groups then developed Consensus Statements and Clinical Recommendations. These were discussed in a plenary and finalized in Delphi rounds. Results A total of 21 Consensus Statements were developed from the systematic reviews. Additionally, the group developed 17 Clinical Recommendations based on the Consensus Statements and the combined expertise of the participants. Conclusions Zygomatic implants are mainly indicated in cases with maxillary bone atrophy or deficiency. Long-term mean zygomatic implant survival was 96.2% [95% CI 93.8; 97.7] over a mean follow-up of 75.4 months (6.3 years) with a follow-up range of 36–141.6 months (3–11.8 years). Immediate loading showed a statistically significant increase in survival over delayed loading. Sinusitis presented with a total prevalence of 14.2% [95% CI 8.8; 22.0] over a mean 65.4 months follow-up, representing the most common complication which may lead to zygomatic implant loss. The international experts suggested clinical recommendations regarding planning, surgery, restoration, outcomes, and the patient’s perspective.

Abstract Purpose The purpose of this study was to perform a systematic review with meta-analysis on the long-term survival rates of zygomatic implants (ZI). ZI success, prostheses survival and success, sinus pathology and patient reported outcomes were also investigated. Methods Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines were followed. Embase and OvidMedline databases were searched alongside the grey literature. The systematic review was recorded in PROSPERO (CRD42022358024). Studies reporting titanium/titanium alloy ZI survival data, ZI-supported prosthesis data, ZIs directly compared to any other implant therapy including grafted sites, a minimum follow-up time of 3 years and a minimum number of 10 patients were included. All study designs were considered if they met the inclusion criteria. Studies not involving ZIs, ZIs not made from titanium/titanium alloy, a follow-up time of

Abstract Purpose To assess the implant and prosthesis survival rates, the clinical, radiographical and patient-related outcome measures, and the masticatory performance of maxillary overdentures supported by two implants in patients with an atrophic maxilla. Methods In this case series, 15 consecutive patients who were eligible for maxillary implant overdenture therapy, but who had insufficient bone volume to place at least four implants and were unwilling to be treated with reconstructive surgery were asked to participate. After giving consent, participants received two implants in the maxilla under local anaesthesia. After 3 months of osseointegration, a maxillary overdenture with palatal coverage and solitary attachments was fabricated. Implant and overdenture survival, marginal bone level change, clinical outcome measures, masticatory performance and patient-related outcomes were evaluated at baseline and 1 year after overdenture placement. Results Fourteen out of 15 participants completed the follow-up period of 12 months. Implant and overdenture survival rate were 89.3% and 85.7%, respectively. Change in marginal bone level (− 0.5 ± 0.7 mm), change in probing depth (0.0 ± 1.0 mm), and clinical outcomes were favourable. Masticatory performance and patient-related outcomes improved significantly compared to baseline. Complications were minimal. Conclusions Within the limitations of this study, it can be concluded that patients with extreme resorption of the maxilla that are unwilling to be treated with reconstructive surgery, benefit from two-implant maxillary overdentures retained by solitary attachments in terms of improved masticatory functioning and denture satisfaction. However, they have relatively high risk of implant loss. Trial registration: UMCG Trial Register (RR201900060), registered 22 January 2019. Graphical Abstract

Applying biodegradable osteosyntheses avoids the disadvantages of titanium osteosyntheses. However, foreign-body reactions remain a major concern and evidence of complete resorption is lacking. This study compared the physico-chemical properties, histological response and radiographs of four copolymeric biodegradable osteosynthesis systems in a goat model with 48-months follow-up. The systems were implanted subperiosteally in both tibia and radius of 12 Dutch White goats. The BioSorb FX [poly(70LLA-co-30DLLA)], Inion CPS [poly([70–78.5]LLA-co-[16–24]DLLA-co-4TMC)], SonicWeld Rx [poly(DLLA)], LactoSorb [poly(82LLA-co-18GA)] systems and a negative control were randomly implanted in each extremity. Samples were assessed at 6-, 12-, 18-, 24-, 36-, and 48-month follow-up. Surface topography was performed using scanning electron microscopy (SEM). Differential scanning calorimetry and gel permeation chromatography were performed on initial and explanted samples. Histological sections were systematically assessed by two blinded researchers using (polarized) light microscopy, SEM and energy-dispersive X-ray analysis. The SonicWeld Rx system was amorphous while the others were semi-crystalline. Foreign-body reactions were not observed during the complete follow-up. The SonicWeld Rx and LactoSorb systems reached bone percentages of negative controls after 18 months while the BioSorb Fx and Inion CPS systems reached these levels after 36 months. The SonicWeld Rx system showed the most predictable degradation profile. All the biodegradable systems were safe to use and well-tolerated (i.e., complete implant replacement by bone, no clinical or histological foreign body reactions, no [sterile] abscess formation, no re-interventions needed), but nanoscale residual polymeric fragments were observed at every system's assessment.

Summary: Background: What baseline predictors would be involved in mortality in people with primary Sjögren syndrome (SjS) remains uncertain. This study aimed to investigate the baseline characteristics collected at the time of diagnosis of SjS associated with mortality and to identify mortality risk factors for all-cause death and deaths related to systemic SjS activity measured by the ESSDAI score. Methods: In this international, real-world, retrospective, cohort study, we retrospectively collected data from 27 countries on mortality and causes of death from the Big Data Sjögren Registry. Inclusion criteria consisted of fulfilling 2002/2016 SjS classification criteria, and exclusion criteria included chronic HCV/HIV infections and associated systemic autoimmune diseases. A statistical approach based on a directed acyclic graph was used, with all-cause and Sjögren-related mortality as primary endpoints. The key determinants that defined the disease phenotype at diagnosis (glandular, systemic, and immunological) were analysed as independent variables. Findings: Between January 1st, 2014 and December 31, 2023, data from 11,372 patients with primary SjS (93.5% women, 78.4% classified as White, mean age at diagnosis of 51.1 years) included in the Registry were analysed. 876 (7.7%) deaths were recorded after a mean follow-up of 8.6 years (SD 7.12). Univariate analysis of prognostic factors for all-cause death identified eight Sjögren-related variables (ocular and oral tests, salivary biopsy, ESSDAI, ANA, anti-Ro, anti-La, and cryoglobulins). The multivariate CPH model adjusted for these variables and the epidemiological features showed that DAS-ESSDAI (high vs no high: HR = 1.68; 95% CI, 1.27–2.22) and cryoglobulins (positive vs negative: HR = 1.72; 95% CI, 1.22–2.42) were independent predictors of all-cause death. Of the 640 deaths with available information detailing the specific cause of death, 14% were due to systemic SjS. Univariate analysis of prognostic factors for Sjögren-cause death identified five Sjögren-related variables (oral tests, clinESSDAI, DAS-ESSDAI, ANA, and cryoglobulins). The multivariate competing risks CPH model adjusted for these variables and the epidemiological features showed that oral tests (abnormal vs normal results: HR = 1.38; 95% CI, 1.01–1.87), DAS-ESSDAI (high vs no high: HR = 1.55; 95% CI, 1.22–1.96) and cryoglobulins (positive vs negative: HR = 1.52; 95% CI, 1.16–2) were independent predictors of SjS-related death. Interpretation: The key mortality risk factors at the time of SjS diagnosis were positive cryoglobulins and a high systemic activity scored using the ESSDAI, conferring a 2-times increased risk of all-cause and SjS-related death. ESSDAI measurement and cryoglobulin testing should be considered mandatory when an individual is diagnosed with SjS. Funding: Novartis.

The objective was to assess the effect of peri-implantitis surgery on the peri-implant microbiome with a follow-up of one year. A total of 25 peri-implantitis patients in whom non-surgical treatment has failed to solve peri-implantitis underwent resective surgical treatment. Their peri-implant pockets were sampled prior to surgical treatment (T0) and one year post treatment (T12). The natural dentition was sampled to analyse similarities and differences with the peri-implantitis samples. Treatment success was recorded. The change in microbial relative abundance levels was evaluated. The microbiota was analysed by sequencing the amplified V3-V4 region of the 16S rRNA genes. Sequence data were binned to amplicon sequence variants that were assigned to bacterial genera. Group differences were analysed using principal coordinate analysis, Wilcoxon signed rank tests, and t-tests. Beta diversity analyses reported a significant separation between peri-implantitis and natural dentition samples on T0 and T12, along with significant separations between successfully and non-successfully treated patients. Eubacterium was significantly lower on T12 compared to T0 for the peri-implantitis samples. Treponema and Eubacterium abundance levels were significantly lower in patients with treatment success on T0 and T12 versus no treatment success. Therefore, lower baseline levels of Treponema and Eubacterium seem to be associated with treatment success of peri-implantitis surgery. This study might aid clinicians in determining which peri-implantitis cases might be suitable for treatment and give a prognosis with regard to treatment success.

Abstract Applying the right torque to osteosynthesis screws is important for undisturbed bone healing. This study aimed to compare test–retest and intra-individual reliabilities of the torque applied to 1.5 mm and 2.0 mm osteosynthesis screws by residents and oral and maxillofacial surgeons (OMF-surgeons), to define the reference torque intervals, and to compare reference torque interval compliances. Five experienced OMF-surgeons and 20 residents, 5 of each 4 residency years, were included. Each participant inserted six 1.5 × 4 mm and six 2.0 × 6 mm screws into a preclinical model at two test moments 2 weeks apart (T1 and T2). Participants were blinded for the applied torque. Descriptive statistics, reference intervals, and intra-class correlation coefficients (ICC) were calculated. The OMF-surgeons complied more to the reference intervals (1.5 mm screws: 95% and 2.0 mm screws: 100%) than the residents (82% and 90%, respectively; P = 0.009 and P = 0.007) with the ICCs ranging between 0.85–0.95 and 0.45–0.97, respectively. The residents’ accuracy and reliability were inadequate regarding the 1.5 mm screws but both measures improved at T2 for both screw types compared to T1, indicating a learning effect. Training residents and/or verifying the applied torque by experienced OMF-surgeons remains necessary to achieve high accuracy and reliability, particularly for 1.5 mm screws.

Abstract Background Primary Sjogren's syndrome (pSS) is a systemic autoimmune disease that is embodied by the loss of salivary gland function and immune cell infiltration, but the mechanism(s) are still unknown. The aim of this study was to understand the mechanisms and identify key factors that leads to the development and progression of pSS. Methods Immunohistochemistry staining, FACS analysis and cytokine levels were used to detect immune cells infiltration and activation in salivary glands. RNA sequencing was performed to identify the molecular mechanisms involved in the development of pSS. The function assays include in vivo saliva collection along with calcium imaging and electrophysiology on isolated salivary gland cells in mice models of pSS. Western blotting, real‐time PCR, alarmin release, and immunohistochemistry was performed to identify the channels involved in salivary function in pSS. Results We provide evidence that loss of Ca2+ signaling precedes a decrease in saliva secretion and/or immune cell infiltration in IL14α, a mouse model for pSS. We also showed that Ca2+ homeostasis was mediated by transient receptor potential canonical‐1 (TRPC1) channels and inhibition of TRPC1, resulting in the loss of salivary acinar cells, which promoted alarmin release essential for immune cell infiltration/release of pro‐inflammatory cytokines. In addition, both IL14α and samples from human pSS patients showed a decrease in TRPC1 expression and increased acinar cell death. Finally, paquinimod treatment in IL14α restored Ca2+ homeostasis that inhibited alarmin release thereby reverting the pSS phenotype. Conclusions These results indicate that loss of Ca2+ signaling is one of the initial factors, which induces loss of salivary gland function along with immune infiltration that exaggerates pSS. Importantly, restoration of Ca2+ signaling upon paquinimod treatment reversed the pSS phenotype thereby inhibiting the progressive development of pSS.

Abstract Objective To systematically review literature about the effect of different implant‐abutment interface designs on peri‐implant bone level changes, implant loss and mid‐buccal mucosa changes around single implants in the anterior maxilla. Reviewing three connection configurations: Platform switched conical (PS‐conical); Platform switched parallel (PS‐parallel); Platform matched parallel (PM‐parallel). Methods A detailed search was carried out in Pubmed, EMBASE, Cochrane, Scopus, Open Gray and African journals Online (until December 1, 2020) and was restricted to clinical prospective studies of at least 1 year and with at least 10 human participants. A meta regression analysis was carried out primarily on the pooled peri‐implant bone level changes followed by implant loss and mid‐buccal mucosa level change. Risk of bias was assessed with RoB 2.0 and ROBINS‐I. The manuscript complied with the PRISMA guidelines and was registered in the PROSPERO database (ID: 225092). Results A total of 5513 hits gave 44 eligible articles for the analyses. Bone level change did not differ significantly between the two platform switched connections; their bone loss scores were significantly lower than PM‐connection. The PS‐conical connections have significantly lower implant losses than the PM connection. Mid‐buccal mucosa level change was comparable between the three connection configurations. Moderate to high risk of bias was detected in the included studies. Conclusions The performance of PS‐conical and PS‐parallel connection configurations both favored bone loss scores compared to the PM‐parallel connection configuration. All three demonstrated mid‐buccal mucosa changes that were small and did not differ significantly amongst the groups.

Abstract Background Cross-sectional studies have shown that elderly with a natural dentition have better general health than edentulous elderly, but this has not been confirmed in studies with longitudinal design. Methods This prospective longitudinal study with a follow-up of 8 years aimed to assess differences in general health, healthcare costs and dental care use between elderly with a natural dentition and edentulous elderly wearing implant-retained or conventional dentures. Based on data of all national insurance claims for dental and medical care from Dutch elderly (aged ≥75 years) general health outcomes (chronic conditions, medication use), healthcare costs and dental care use could be assessed of three groups of elderly, viz. elderly with a natural dentition, elderly with conventional dentures and elderly with implant-retained overdentures. Results At baseline (2009), a total of 168,122 elderly could be included (143,199 natural dentition, 18,420 conventional dentures, 6503 implant-retained overdentures). Here we showed that after 8 years follow-up elderly with a natural dentition had more favorable general health outcomes (fewer chronic conditions, less medication use), lower healthcare costs and lower dental costs – but higher dental care use – than edentulous elderly. At baseline the general health of elderly with an implant-retained overdentures resembled the profile of elderly with a natural dentition, but over time their general health problems became comparable to elderly with conventional dentures. Conclusions It was concluded that elderly with a natural dentition had significant better health and lower healthcare costs compared to edentulous elderly (with or without dental implants).

IntroductionThe relation between rheumatoid arthritis (RA) and periodontitis (PD) has been investigated ever since the discovery of the citrullinating enzyme peptidyl arginine deaminase presents in the oral bacterium Porphyromonas gingivalis. Recently, we demonstrated the presence of RA autoantibodies, especially of IgA anti-citrullinated protein antibody (ACPA), in gingival crevicular fluid (GCF) of Indonesian patients with and without RA or PD which might indicate the local formation of RA antibodies in the periodontium.AimThe purpose of this study was to assess whether the subgingival microbiome is related to the presence of IgA ACPA in the GCF of healthy individuals with or without PD.Patients and MethodsHealthy individuals with a known periodontal status and high IgA ACPA (>0.1 U/ml) in GCF (n = 27) were selected and matched for age, gender, periodontal status, and smoking status with 27 healthy individuals without IgA ACPA in their GCF. Taxonomic profiling of the subgingival microbiome was based on bacterial 16S rRNA gene sequencing. Downstream analyses were performed to assess compositional differences between healthy subjects with or without IgA ACPA in GCF and with or without PD.ResultsBetween groups with or without PD, or with or without IgA ACPA in GCF, no differences in alpha diversity were seen. Beta diversity was different between groups with or without PD (p < 0.0001), and a trend was seen in subjects with PD between subjects with or without IgA ACPA in GCF (p = 0.084). Linear discriminant analysis effect size (LEfSe) revealed no significant differences in the total population between subjects with IgA ACPA compared to subjects without IgA ACPA in GCF. Although Porphyromonas was not identified by LEfSe, its relative abundance was significantly higher in healthy individuals with high IgA ACPA in GCF compared to individuals without IgA ACPA in GCF (p = 0.0363). Zooming in on the subgroup with PD, LEfSe revealed that species Neisseriaceae, Tannerella, and Haemophilus were more abundant in the subjects with IgA ACPA in GCF compared to subjects without IgA ACPA in GCF.ConclusionPeriodontitis and certain taxa, including Porphyromonas, seem to be associated with the local presence of ACPA in the periodontium.

Abstract Background Clinical studies of single-tooth replacement in compromised bone using bone level tapered implants in the aesthetic zone are scarce. Aim To assess clinically, radiographically and aesthetically over 1 year the performance of a bone level tapered implant in the maxillary aesthetic zone in sites after alveolar ridge preservation. Material and methods Thirty patients (16 male, 14 female) with a failing tooth and large bone defect after removal received alveolar ridge preservation. After 3 months, implants were placed with immediate provisionalization. Definitive restorations were placed after 3 months. The treatment was evaluated 1 year following the definitive restoration. Results All the patients attended the 1-year follow-up. One implant was lost (96.7% implant survival rate). The mean implant stability quotient value was 68.9 ± 8.74 at implant placement. The mean marginal bone level change was minor (− 0.07 ± 0.12 mm). The mean mid-buccal mucosa changed with + 0.01 ± 0.45 mm. The median Pink Esthetic Score and White Esthetic Score after 1 year were 6 [4; 7] and 8 [7; 9], respectively. The patients’ mean overall satisfaction (0–100 VAS scale) was 86.6 ± 10.3. Conclusion Bone level tapered implants with immediate provisionalization perform well after alveolar ridge preservation in the maxillary aesthetic zone, according to implant stability, clinical, radiographic, aesthetic and patient-centred outcomes. Trial registration NTR, NL8755 . Registered on 1 January 2016

Abstract The reproducibility of scanning in the periorbital region with 3D technology to enable objective evaluations of surgical treatment in the periorbital region was assessed. Facial 3D-scans of 15 volunteers were captured at different time points with a handheld Artec Space Spider structured light scanner. Two scans were made with a one minute interval and repeated after 1 year; for both a natural head position and with the head in a fixation-device. On assessing the area between the eyelashes and eyebrows, the medians of the average deviations between the various cross-sections of the one minute interval 3D-scans ranged from 0.17 to 0.21 mm at baseline, and from 0.10 to 0.11 mm when the minute-interval scanning was repeated one year later. The systematic differences when scanning in a natural head position and fixated position were comparable. The reproducibility of the 3D processing was excellent (intraclass correlation coefficient > 0.9). The repeated scanning deviations (baseline versus one year data) were well within the accepted clinical threshold of 1 mm. Scanning with a hand-held 3D-scanning device (Artec Space Spider) is a promising tool to assess changes in the periorbital region following surgical treatment since the median deviations are well below the clinically accepted 1 mm measuring error, for both the natural head and fixated positions.

Abstract Background Calvarial bone grafts as a pre-implant augmentation procedure are mostly used to reconstruct the edentulous maxilla, although calvarial grafts could also be used in the partially dentate patients needing extensive bone grafting. Methods In 7 consecutive partially dentate patients needing bone grafting because of a large bony defect as a result of trauma (n = 1), oligodontia (n = 1), failed previous bone augmentation (n = 1), or atrophy (n = 4), the alveolar process was reconstructed with calvarial bone as a pre-implant procedure. Results A total of 30 implants was placed either immediate at the time of bone grafting (13 implants) or after a healing time of 4 months when immediate placement was not possible (17 implants). One wound dehiscence occurred that needed secondary intervention. During follow-up (40 ± 14 months), one implant was lost due to peri-implantitis with an infected osteosynthesis screw. Marginal peri-implant bone loss was 0.65 ± 0.47 mm during this period. Conclusion Calvarial bone is a sound extra-oral donor site when aiming for reconstruction of a large bony defect of the alveolar process of partially dentate patients.

Primary Sjogren’s syndrome (pSS) is a systemic autoimmune disease that is characterized by the infiltration of immune cells. Although the loss of salivary gland function is a major manifestation observed in pSS, the factors that could promote these changes in salivary gland tissue in pSS is not yet determined. Herein, we provide evidence that loss of alpha-1 antiproteinase antitrypsin could contribute to the induction of pSS. Alpha-1 antiproteinase antitrypsin belongs to the family of serpin proteins that function as protease inhibitors and protect secretory cells against proteases, especially to elastases that is secreted from lymphocytes. Importantly, expression of alpha-1 antiproteinase antitrypsin was decreased (more than 3-fold), along with an increase in elastase expression, in pSS samples when compared with age-matched non-SS-SICCA patients. Consistent with the human data, loss of alpha-1 antiproteinase antitrypsin, as well as an increase in immune infiltration, was observed in IL14α transgenic mice that exhibit SS like symptoms. Moreover, an age-dependent increase in elastase expression was observed in IL14α transgenic mice along with a decrease in total saliva secretion. Importantly, a 4-fold increase in microRNA132 expression, but not in other microRNAs, and increased DNA methylation in the promoter/noncoding region of serpina gene was observed in pSS, which could be responsible for the inhibition of alpha-1 antiproteinase antitrypsin expression in salivary gland cells of pSS patients. Together, these findings demonstrate that epigenetic regulations that include DNA methylation and microRNAs that could modulate the expression of alpha-1 antiproteinase antitrypsin in salivary glands and could be involved in the onset of pSS.

Abstract Background Templates aim to facilitate implant placement in the prosthetically preferred position. Mucosa-supported and bone-supported templates are commonly used in the edentulous maxilla. In the atrophic maxilla (Cawood V and VI), however, these templates can be easily displaced due to a lack of supportive tissues, even in cases where anterior sites offer sufficient bone for implant placement. To assist in positioning and stabilisation, we designed a template that utilises the nasal aperture as a fulcrum to create a forced and exclusive fit. The aim of this study was to assess the clinical usability of the developed template and the corresponding implant placement accuracy in patients with edentulous atrophic maxillae. Deviations between planned and placed implant positions were measured by aligning pre- and post-operative cone beam computed tomography scans. Results Twenty-four implants were placed in 11 patients. One template did not fit properly due to a slight undercut. All implants could be placed with good primary stability. The implants had high accuracy at the implant shoulder (global deviation 1.1 ± 0.5 mm, lateral deviation 0.8 ± 0.5 mm) and a mean angular deviation of 7.2 ± 3.4°. Conclusions The developed surgical template offers stabilised and secure template placement in the edentulous atrophic maxilla, resulting in satisfying implant placement accuracy when using a semi-guided approach. Trial registration Netherlands Trial Register, NL6561 , registered 26 September 2017.

Introduction. Immediate implant placement and immediate chairside provisionalization in the esthetic zone require meticulous treatment planning. A digital workflow that combines intraoral scans and a cone beam computed tomography scan can be used to visualize the surgical and restorative aspects of the treatment and to plan a prosthetically driven implant position. A digital workflow in implant dentistry enables the prefabrication of an individualized CAD/CAM temporary restoration, based on the planned implant position. This could be a predictable method to deliver a screw-retained temporary restoration, directly after static computer-assisted immediate implant surgery. Interventions. Three patients with a failing tooth in the maxillary esthetic zone were treated with immediate implant placement and chairside provisionalization using this digital workflow. After 3 months, a final restoration was placed. Clinical, radiographic, and patient-reported outcome measures were collected prior to implant treatment, 6 weeks after placing the temporary restoration and then 1 month and 1 year after placing the final restoration. Outcomes. At the 1-year follow-up, healthy soft tissues were observed, and peri-implant bone levels were stable. Patient satisfaction after the treatment was high. Conclusion. The three reported cases demonstrate the potential for predictable immediate implant placement and chairside provisionalization using a digital workflow.

BackgroundWhile 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.MethodsParaffin-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.ResultsWith 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 (FDR1) 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

Abstract Background Little is known about the impact of bone graft harvesting for pre-implant augmentation of the maxilla from a patient’s perspective. To assess patient-reported outcome measures (PROMs) related to augmentation of the extremely resorbed edentulous maxilla with calvarial or anterior iliac crest bone. Materials and methods For this randomised controlled trial, 20 consecutive edentulous patients needing extensive pre-implant surgery of the maxilla were randomly assigned to either calvarial (n = 10) or anterior iliac crest (n = 10) bone harvesting. Patient reports on procedure-related satisfaction, questionnaires on oral functionality (denture satisfaction, chewing ability) and oral health-related quality of life (OHIP-49NL) and subjective donor site-related outcomes (e.g. of post-operative pain, scar formation, physical mobility) were assessed. Results Irrespective of the harvesting site, patients were generally satisfied (median VAS score 93 (86–99) mm, p = 0.400) with the procedure and its final results. Post-operative pain was mild (median 40 (20–40) mm) and decreased to no pain (4 (0–16) mm) within 14 days. Early post-operative pain was significantly higher following anterior iliac crest harvesting (p

Osteosynthesis systems are used to fixate bone segments in maxillofacial surgery. Titanium osteosynthesis systems are currently the gold standard. However, the disadvantages result in symptomatic removal in up to 40% of cases. Biodegradable osteosynthesis systems, composed of degradable polymers, could reduce the need for removal of osteosynthesis systems while avoiding the aforementioned disadvantages of titanium osteosyntheses. However, disadvantages of biodegradable systems include decreased mechanical properties and possible foreign body reactions. In this review, the literature that focused on the in vitro and in vivo performances of biodegradable and titanium osteosyntheses is discussed. The focus was on factors underlying the favorable clinical outcome of osteosyntheses, including the degradation characteristics of biodegradable osteosyntheses and the host response they elicit. Furthermore, recommendations for clinical usage and future research are given. Based on the available (clinical) evidence, biodegradable copolymeric osteosyntheses are a viable alternative to titanium osteosyntheses when applied to treat maxillofacial trauma, with similar efficacy and significantly lower symptomatic osteosynthesis removal. For orthognathic surgery, biodegradable copolymeric osteosyntheses are a valid alternative to titanium osteosyntheses, but a longer operation time is needed. An osteosynthesis system composed of an amorphous copolymer, preferably using ultrasound welding with well-contoured shapes and sufficient mechanical properties, has the greatest potential as a biocompatible biodegradable copolymeric osteosynthesis system. Future research should focus on surface modifications (e.g., nanogel coatings) and novel biodegradable materials (e.g., magnesium alloys and silk) to address the disadvantages of current osteosynthesis systems.

A major complication of primary Sjögren's syndrome (pSS) is development of mucosa associated lymphoid tissue (MALT) B-cell lymphoma, particularly in salivary glands. These lymphomas express FcRL4 and are characteristically associated with lymphoepithelial lesions. Neoplastic B-cells may be derived from non-neoplastic glandular intraductal B-cells, also virtually all expressing FcRL4. A characteristic feature of MALT lymphomas is the production of rheumatoid factors (RFs), which are largely encoded by stereotypic immunoglobulin variable heavy chain (IGHV) sequences. The aim of this study was to examine whether there is a relationship between the intraductal and periductal B-cells and whether the intraductal B-cells are selected for RF. RNA was extracted from laser-microdissected infiltrated ductal areas and periductal infiltrates from frozen parotid gland tissue sections of 5 pSS patients. PCR amplified IGHV transcripts were cloned into pCR™4-TOPO vector and subsequently sequenced. Microdissected ducts yielded 96 unique IGHV sequences derived from intraductal B-cells, while 119 unique IGHV sequences were obtained from periductal infiltrates. No major difference in VH-gene usage was observed between intraductal and periductal B-cells. Nearly all (>90%) IGHV sequences derived from both intraductal and periductal B-cells were mutated. Clonal expansions as defined by shared VDJ rearrangements were also present among both intraductal and periductal B-cells: in total 32 clones were found, from which 12 were located within ducts, 15 in periductal areas, and five clones shared members in both areas. We observed 12 IGHV rearrangements encoding for RF sequences from which two were derived from intraductal B-cells and 10 from periductal B-cells. Nine RF sequences were part of a clone. Together these findings indicate that intraductal and periductal B-cells are closely related to each other. Intraductal B-cells are most likely derived from periductal B-cells. We did not obtain evidence that RF-specific B-cells are enriched within the striated ducts. We speculate that in principle any activated B-cell can enter the striated ducts from the periductal infiltrate, irrespective of its antigenic specificity. Within the ducts, these B-cells may receive additional activation and proliferation signals, to further expand at these sites and by acquisition of driver-mutations develop toward lymphoma.

Background: Salivary glands (SGs) can be damaged by immune checkpoint inhibitor (ICI) therapy. In patients with ICI-induced SG dysfunction, 60% progress to fulfill classification criteria for primary Sjögren's syndrome (pSS), owing to immune foci in SGs and/or anti-SSA autoantibody positivity. We report the SG tissue analysis of a patient with SG dysfunction after treatment with a programmed death ligand-1 (PD-L1) inhibitor, compared to that of a dry mouth (“sicca”) control and pSS patient.Case presentation: The patient received the PD-L1 inhibitor durvalumab (10 mg/kg, every 2 weeks by intravenous infusion) as adjuvant treatment for stage 3 non-small cell lung carcinoma, following concurrent chemo radiotherapy. At 43 weeks after 21 cycles of Durvalumab, the patient was not capable of producing unstimulated or stimulated parotid gland saliva, and a biopsy was taken. Immunohistochemical analysis showed no classical AQP5+ CK7− acinar cell clusters (CK7 marks intercalated ducts, IDs). In contrast, the parenchyma was dominated by hybrid epithelial “structures” with ID-like morphology, containing a mixture of AQP5+CK7−, AQP5−CK7+, and AQP5+CK7+ cells (30 structures/mm2). These structures were present at lower frequencies in sicca control (2/mm2) and pSS (10/mm2) tissue. Hybrid structures contained proliferating (Ki67+) cells and senescent (p16+) cells. Striated ducts showed no abnormal morphology post PD-L1 treatment, in contrast to pSS tissue. PD-L1 expression was detected in the SG parenchyma following anti-PD-L1 therapy. The SG post-PD-L1 therapy further demonstrated focal lymphocytic sialadentitis, harboring disperse, and focal CD4+ T cell-rich infiltrates. CD8+ T cells were also present. In this patient, these CD4+ and CD8+ T cells were observed in-between and inside hybrid structures. CD20+ B-cells were infrequently detected following PD-L1 blockade, in contrast to their preponderance in pSS SG tissue.Conclusion: This patient lacked conventional SG acinar cells following anti-PD-L1 therapy and demonstrated presence of hybrid intercalated duct-like structures. Understanding which mechanisms and dynamics underpinning this aberrant parenchyma may be crucial to understand how SG dysfunction post ICI therapy, and potentially other affected organs. Furthermore, although the patient treated with anti-PD-L1 antibody examined here fulfills the criteria for pSS and demonstrated focal lymphocytic sialadentitis, the further histopathological characteristics do not resemble pSS.

Objective. To assess the clinical, radiographic, aesthetic, and patient-centred outcomes of a new implant system applied for an immediate implant placement and restoration approach in single tooth replacement of anterior maxillary teeth. Material and Method. Three cases were treated with a bone level tapered implant. All patients were treated with the same strategy involving flapless extraction and implant placement with simultaneous augmentation. Implants were provisionally restored with a screw-retained restoration at the day of surgery. Definitive restoration was fabricated after 3 months. Follow-up was one year after definitive restoration. Results. At the 1-year follow-up, the implants were stable and no complications had occurred. Peri-implant bone levels had increased with a mean value of 0.24±0.30 mm between definitive restoration placement and 1 year of follow-up. Clinical outcome scores showed healthy soft tissues. Mean Pink and White Esthetic scores were rated 7.0 and 7.3, respectively. Mean patient satisfaction had improved from 55.7 (pretreatment) to 90.0 (1-year follow-up) on a 0-100 VAS scale. Conclusion. Immediate implant placement and restoration with the new tapered bone level implant system are accompanied by good initial clinical and radiographic results as well as high patient satisfaction.

Abstract Background The aim of computer-designed surgical templates is to attain higher precision and accuracy of implant placement, particularly for compromised cases. Purpose The purpose of this study is to show the benefit of a full three-dimensional virtual workflow to guide implant placement in oligodontia cases where treatment is challenging due compromised bone quantity and limited interdental spaces. Patient and methods A full, digitalized workflow was performed for implant placement in two oligodontia patients. Accuracy was assessed by calculating the coordinates of the entry point (shoulder) and apex (tip) as well as the angular deviation of the planned and actual implants. Results Implant placement could be well performed with the developed computer-designed templates in oligodontia. Mean shoulder deviation was 1.41 mm (SD 0.55), mean apical deviation was 1.20 mm (SD 0.54) and mean angular deviation was 5.27° (SD 2.51). Conclusion Application of computer-designed surgical templates, as described in this technical advanced article, aid in predictable implant placement in oligodontia where bone quantity is scarce and interdental spaces are limited.

Summary:. Weight gain can affect the volume of a facial fat graft, resulting in unfavorable asymmetries. Weight gain during pregnancy is more complex and does not just entail an increase in adipose tissue. This case report objectifies whether pregnancy results in volume changes of a facial fat graft. A 24-year-old woman received a fat graft (7 ml) in the mandibular area to mask a volume deficiency. This deficiency occurred after a fibula reconstruction of a mandibular defect resulting from the removal of an ameloblastoma. The patient became pregnant 3 weeks after the fat graft procedure. Standardized 3-dimensional photographs (3dMD) were available preoperatively and at 7 weeks (first trimester), 6 months (second trimester), 9 months (third trimester), and 14 months (4 months after delivery) postoperatively. Three-dimensional analysis revealed that no substantial volume changes of the fat graft occurred during pregnancy other than the overall proportional gain in facial volume. Pregnancy apparently does not affect the volume of a small unilateral fat graft applied in the facial region.

Previous studies revealed high incidence of acquired N-glycosylation sites acquired N-glycosylation sites in RNA transcripts encoding immunoglobulin heavy variable region (IGHV) 3 genes from parotid glands of primary Sjögren’s syndrome (pSS) patients. In this study, next generation sequencing was used to study the extent of ac-Nglycs among clonally expanded cells from all IGVH families in the salivary glands of pSS patients. RNA was isolated from parotid gland biopsies of five pSS patients and five non-pSS sicca controls. IGHV sequences covering all functional IGHV genes were amplified, sequenced, and analyzed. Each biopsy recovered 1,800–4,000 unique IGHV sequences. No difference in IGHV gene usage was observed between pSS and non-pSS sequences. Clonally related sequences with more than 0.3% of the total number of sequences per patient were referred to as dominant clone. Overall, 70 dominant clones were found in pSS biopsies, compared to 15 in non-pSS. No difference in percentage mutation in dominant clone-derived IGHV sequences was seen between pSS and non-pSS. In pSS, no evidence for antigen-driven selection in dominant clones was found. We observed a significantly higher amount of ac-Nglycs among pSS dominant clone-derived sequences compared to non-pSS. Ac-Nglycs were, however, not restricted to dominant clones or IGHV gene. Most ac-Nglycs were detected in the framework 3 region. No stereotypic rheumatoid factor rearrangements were found in dominant clones. Lineage tree analysis showed in four pSS patients, but not in non-pSS, the presence of the germline sequence from a dominant clone. Presence of germline sequence and mutated IGHV sequences in the same dominant clone provide evidence that this clone originated from a naïve B-cell recruited into the parotid gland to expand and differentiate locally into plasma cells. The increased presence of ac-Nglycs in IGHV sequences, due to somatic hypermutation, might provide B-cells an escape mechanism to survive during immune response. We speculate that glycosylation of the B-cell receptor makes the cell sensitive to environmental lectin signals to contribute to aberrant B-cell selection in pSS parotid glands.

To systematically review the literature comparing the efficacy and safety of dexmedetomidine and midazolam when used for procedural sedation.We searched MEDLINE, EMBASE and COCHRANE for clinical trials comparing dexmedetomidine and midazolam for procedural sedation up to June 20, 2016. Inclusion criteria: clinical trial, human subjects, adult subjects (≥18 years), article written in English, German, French or Dutch, use of study medication for conscious sedation and at least one group receiving dexmedetomidine and one group receiving midazolam. Exclusion criteria: patients in intensive care, pediatric subjects and per protocol use of additional sedative medication other than rescue medication. Outcome measures for efficacy comparison were patient and clinician satisfaction scores and pain scores; outcome measures for safety comparison were hypotension, hypoxia, and circulatory and respiratory complications.We identified 89 papers, of which 12 satisfied the inclusion and exclusion criteria; 883 patients were included in these studies. Dexmedetomidine was associated with higher patient and operator satisfaction than midazolam. Patients receiving dexmedetomidine experienced less pain and had lower analgesic requirements. Respiratory and hemodynamic safety were similar.Dexmedetomidine is a promising alternative to midazolam for use in procedural sedation. Dexmedetomidine provides more comfort during the procedure for the patient and clinician. If carefully titrated, the safety profiles are similar.

As the population ages, the risk of becoming malnourished increases. Research has shown that poor oral health can be a risk factor for malnutrition in institutionalized elderly. However, it remains unclear whether oral health problems, edentulousness and health-related quality of life also pose a risk for malnutrition in community-dwelling older adults. In this cross-sectional observational study, 1325 community-living elderly (≥75 years) were asked to complete questionnaires regarding nutritional status, oral status (edentulous, remaining teeth, or implant-supported overdentures), oral health problems, health-related quality of life (HRQoL), frailty, activities of daily living (ADL) and complexity of care needs. Univariate and multivariate logistic regression analyses were performed with nutritional status as dependent variable. Of the respondents, 51% (n = 521) were edentulous, 38.8% (n = 397) had remaining teeth and 10.2% (n = 104) had an implant-supported overdenture. Elderly with complex care needs were malnourished most frequently, followed by frail and robust elderly (10%, 4.5% and 2.9%, respectively). Malnourished elderly reported more frequent problems with chewing and speech when compared with well-nourished elderly (univariate analysis). However, multivariate analysis did not show an association between malnutrition and oral health problems and edentulousness, although HRQoL was associated with malnutrition (odds ratio (OR) 0.972, confidence interval (CI) 0.951⁻0.955). Based on the results of this cross-sectional study, it can be concluded that poor HRQoL is significantly associated with malnutrition; however, edentulousness and oral health problems are not.

OBJECTIVE:Seropositive arthralgia patients (SAP) are at high risk of developing rheumatoid arthritis (RA). This prospective study aimed to determine whether altered peripheral regulatory T-cells (Tregs) and defined subsets, besides a broadened anti-citrullinated protein antibody (ACPA) response, may qualify as biomarkers for RA development in SAP. METHODS:Thirty-four consecutive SAP were prospectively assessed every 6 months for minimally 2 years. At inclusion, peripheral Treg (CD4+CD25+FoxP3+) numbers and subsets, defined as CD45RA+FoxP3low naive Tregs (Fr I), CD45RA-FoxP3high activated Tregs (Fr II) and CD45RA-FoxP3low non-Tregs (Fr III), were compared to age- and sex-matched healthy controls (HC, n = 16) and treatment-naive RA patients (n = 12). SAP that developed RA were compared to non-switchers and analyzed for Treg numbers and Treg subsets at inclusion. Also, Treg numbers and subsets were compared in switched SAP before and at diagnosis. To assess the ACPA repertoire, IgG and IgA reactivity was measured against citrullinated peptides from fibrinogen, α-enolase and vimentin. RESULTS:Treg numbers were similar between HC, SAP and RA patients. Although the bonafide Treg subsets Fr I and Fr II were comparable between groups, Fr III was increased in SAP compared to HC (p = 0.01). Fourteen (41%) SAP developed RA during follow-up. Their Treg numbers and subsets were comparable to non-switched SAP. At RA diagnosis, Treg numbers in switched SAP were similar to 6 months before. Switched SAP displayed a more diverse IgG ACPA repertoire compared to non-switched SAP (p = 0.046) and showed more IgA reactivity than non-switched SAP reaching significance for Fib1 only (p = 0.047). CONCLUSION:Numbers of Total Treg and bonafide Treg subsets are not indicative for RA development in SAP, opposed to the ACPA repertoire.

Water forms the basis of lubrication in the human body, but is unable to provide sufficient lubrication without additives. The importance of biolubrication becomes evident upon aging and disease, particularly under conditions that affect secretion or composition of body fluids. Insufficient biolubrication, may impede proper speech, mastication and swallowing, underlie excessive friction and wear of articulating cartilage surfaces in hips and knees, cause vaginal dryness, and result in dry, irritated eyes. Currently, our understanding of biolubrication is insufficient to design effective therapeutics to restore biolubrication. Aim of this study was to establish the role of structure and glycosylation of adsorbed protein films in biolubrication, taking the oral cavity as a model and making use of its dynamics with daily perturbations due to different glandular secretions, speech, drinking and eating, and tooth brushing. Using different surface analytical techniques (a quartz crystal microbalance with dissipation monitoring, colloidal probe atomic force microscopy, contact angle measurements and X-ray photo-electron spectroscopy), we demonstrated that adsorbed salivary conditioning films in vitro are more lubricious when their hydrophilicity and degree of glycosylation increase, meanwhile decreasing their structural softness. High-molecular-weight, glycosylated proteins adsorbing in loops and trains, are described as necessary scaffolds impeding removal of water during loading of articulating surfaces. Comparing in vitro and in vivo water contact angles measured intra-orally, these findings were extrapolated to the in vivo situation. Accordingly, lubricating properties of teeth, as perceived in 20 volunteers comprising of equal numbers of male and female subjects, could be related with structural softness and glycosylation of adsorbed protein films on tooth surfaces. Summarizing, biolubrication is due to a combination of structure and glycosylation of adsorbed protein films, providing an important clue to design effective therapeutics to restore biolubrication in patients with insufficient biolubrication.