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 Sjögren's Disease (SjD) patients.

Radiation-induced Xerostomia is Related to Stem Cell Dose-dependent Reduction of Saliva Production.

PURPOSE: Previous studies have shown that the mean dose to the parotid gland stem cell rich regions (Dmean,SCR) is the strongest dosimetric predictor for the risk of patient-reported daytime xerostomia. This study aimed to test whether the relationship between patient-reported xerostomia and Dmean,SCR is explained by a dose-dependent reduction of saliva production. METHODS AND MATERIALS: In 570 patients with head and neck cancer treated with definitive radiation therapy (RT), flow from the parotid (FLOWPAR) and submandibular/sublingual (FLOWSMSL) glands, and patient-reported daytime (XERDAY) and nighttime (XERNIGHT) xerostomia were prospectively measured before, at 6 months, and 12 months after RT. Using linear mixed effect models, the relationship of the mean dose to the parotid glands (Dmean,par), Dmean,SCR, non-SCR parotid gland tissue (Dmean,non-SCR), submandibular glands (Dmean,sub), and oral cavity (Dmean,oral) with salivary flow and xerostomia was analyzed while correcting for known confounders. RESULTS: Dmean,SCR proved to be responsible for the effect of Dmean,par on FLOWPAR (P ≤ .03), while Dmean,non-SCR did not affect FLOWPAR (P ≥ .11). To illustrate, increasing Dmean,SCR by 10 Gy at a fixed Dmean,non-SCR reduced FLOWPAR by 0.02 mL/min (25%) after RT. However, if the opposite happened, no change in FLOWPAR was observed (0.00 mL/min [4%]). As expected, Dmean,sub was significantly associated with FLOWSMSL (P < .001). For example, increasing Dmean,sub by 10 Gy reduced FLOWSMSL by 0.07 mL/min (26%) after RT. Xerostomia scores were also affected by dose to the salivary glands. Dmean,SCR and Dmean,oral were associated with higher XERDAY scores (P ≤ .05), while Dmean,sub increased XERNIGHT scores (P = .01). For example, an increase of 10 Gy in Dmean,SCR raised XERDAY scores by 2.13 points (5%) after RT, while an additional 10 Gy in Dmean,subs increased XERNIGHT scores by 2.20 points (6%) after RT. Salivary flow was not only associated with radiation dose, but also with xerostomia scores in line with the salivary glands' functions; ie, FLOWPAR only influenced XERDAY (P < .001, 10.92 points lower XERDAY per 1 mL/min saliva), while FLOWSMSL affected XERDAY and XERNIGHT (P ≤ .004, 6.69 and 5.74 points lower XERDAY and XERNIGHT, respectively, per 1 mL/min saliva). Therefore, the observed relationships between dose and xerostomia were corrected for salivary flow. As hypothesized, Dmean,SCR only increased XERDAY scores via reducing FLOWPAR, whereas the effects of Dmean,oral on XERDAY and Dmean,sub on XERNIGHT were independent of salivary flow. CONCLUSIONS: Higher SCR region dose reduced parotid gland saliva production, subsequently resulting in higher daytime xerostomia scores. Consequently, this study supports the clinical implementation of stem cell sparing RT to preserve salivary flow with the aim of reducing the risk of xerostomia.

Histopathological comparison of Sjögren-related features between paired labial and parotid salivary gland biopsies of sicca patients.

OBJECTIVES: To compare focus score (FS) and other histopathological features between paired labial and parotid salivary gland biopsies in a diagnostic cohort of suspected Sjögren's disease (SjD) patients. METHODS: Labial and parotid salivary gland biopsies were simultaneously obtained from patients with sicca complaints, suspected of having SjD. Biopsies were formalin fixed and paraffin embedded. Sections were stained with haematoxylin & eosin (H&E) and for CD3, CD20, CD45, cytokeratin, CD21, Bcl6, activation induced deaminase (AID), and IgA/IgG. FS and other histopathological features characteristic for SjD were analysed. RESULTS: Based on the expert opinion of three experienced rheumatologists, 36 patients were diagnosed as SjD and 63 as non-SjD sicca patients. When taking all patients together, absolute agreement of various histopathological features between labial and parotid biopsies was high and varied between 80% (FS) and 93% ((pre-)lymphoepithelial lesions (LELs)). More labial gland biopsies had a FS ≥ 1 compared with their parotid counterpart. Accordingly, the area of infiltrate was larger in labial gland biopsies. When considering only SjD patients, labial glands contained significantly less B-lymphocytes, GCs/mm2 and less severe LELs compared with parotid glands. CONCLUSION: Labial and parotid glands from SjD patients contain similar histopathological key features, and thus both glands can be used for diagnosis and classification of SjD. However, parotid salivary glands reveal more evident B-lymphocyte related features, while labial glands exhibit more inflammation, which may be partially unrelated to SjD.

Immediate implant placement with immediate or delayed provisionalization in the maxillary aesthetic zone: A 10-year randomized trial.

AIM: To compare the marginal bone level of immediately placed implants, with either immediate or delayed provisionalization (IP or DP), in the maxillary aesthetic zone after 10 years of function. MATERIALS AND METHODS: Participants with a failing tooth in the maxillary aesthetic zone were randomly assigned to immediate implant placement with either IP (n = 20) or DP (n = 20) after primary wound closure with a free gingival graft. The final restoration was placed 3 months after provisionalization. The primary outcome was change in marginal bone level. In addition, implant survival, restoration survival and success, peri-implant tissue health, mucosa levels, aesthetic indices, buccal bone thickness and patient satisfaction were evaluated. RESULTS: After 10 years, the mean mesial and distal changes in marginal bone level were -0.47 ± 0.45 mm and -0.49 ± 0.52 mm in the IP group and -0.58 ± 0.76 mm and -0.41 ± 0.72 mm in the DP group (p = .61; p = .71). The survival rate was 100% for the implants; for the restorations, it was 88.9% in the IP group and 87.5% in the DP group. Restoration success, according to modified USPHS criteria, was 77.8% in the IP group and 75.0% in the DP group. The prevalence of peri-implant mucositis was 38.9% and 35.7% and of peri-implantitis 0.0% and 6.3%, respectively, in the IP group and DP group (p = 1.0; p = .40). The Pink Esthetic Score and White Esthetic Score was 15.28 ± 2.32 in the IP group and 14.64 ± 2.74 in the DP group, both clinically acceptable (p = .48). The buccal bone thickness was lower in the DP group. Patient satisfaction was similar in both groups (p = .75). CONCLUSIONS: The mean marginal bone level changes after immediate implant placement with IP were similar to those after immediate placement with DP. CLINICAL TRIAL REGISTRATION: Registered in the National Trial Register (NL9340).

The Peri-Implant Microbiome-A Possible Factor Determining the Success of Surgical Peri-Implantitis Treatment?

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.

Single crowns in the posterior maxilla supported by either 11-mm long implants with sinus floor augmentation or by 6-mm long implants: A 10-year randomized controlled trial.

OBJECTIVES: To compare the clinical performance of single crowns in the posterior maxilla supported by either 11-mm long implants combined with maxillary sinus floor augmentation (MSFA) surgery or by 6-mm long implants during a 10-year follow-up period. MATERIALS AND METHODS: Subjects were randomly allocated to receive one 11-mm long implant in combination MFSA or to receive one 6-mm long implant without any grafting. Twenty-one implants in 20 patients were placed in the 6-mm group and 20 implants in 18 patients were placed in the 11-mm group. Both groups were followed by clinical and radiographic examinations up to 10 years. Patients' satisfaction was also scored before treatment. RESULTS: Two patients died and eight patients moved during the follow-up. Two patients lost an implant in the 6-mm group and one implant was lost in the 11-mm group (implant survival 89.5% and 90.9%, respectively). From loading to 10 years' follow-up, mean ± SE marginal bone loss in the 6-mm group and 11-mm group was 0.18 ± 0.10 mm and 0.26 ± 0.12 mm, respectively, without a significant difference between the groups at 10 years (p = .650). In both groups, indices scores for plaque, calculus, gingiva and bleeding were low as well as mean pocket probing depth. Patients' satisfaction at 10 years was high in both groups; mean overall satisfaction in the 6-mm group and 11-mm group was 9.6 ± 0.6 and 9.2 ± 0.8, respectively (p = .168). CONCLUSIONS: Placement of 6-mm implants or 11-mm implants combined MFSA are equally successful during a 10-year follow-up period when applied for supporting a single restoration.

Increased Diagnostic Accuracy of the Labial Gland Biopsy in Primary Sjögren Syndrome When Multiple Histopathological Features Are Included.

OBJECTIVE: The aim of this study was to evaluate the diagnostic accuracy of the labial salivary gland biopsy based on multiple histopathological features in patients with suspected primary Sjögren syndrome (pSS). METHODS: Patients from a diagnostic sicca cohort with clinically suspected pSS who underwent a labial gland biopsy were included. Patients were categorized as having pSS or non-Sjögren syndrome sicca (non-SS sicca) based on vignettes scored by an expert panel. Labial gland biopsies were analyzed for the presence of four histopathological features: focus score (FS) ≥1, prelymphoepithelial and lymphoepithelial lesions, immunoglobulin G plasma cell shift, and germinal centers. Sensitivity and specificity of histologic features were calculated, and the optimal cutoff value for the number of histopathological features needed to diagnose pSS was determined with receiver operating curve analysis. RESULTS: A total of 38 patients were categorized as having pSS and 65 as having non-SS sicca. In labial gland biopsies of patients with pSS, the prevalence of FS ≥1 was 82%, followed by 68% for pre-lymphoepithelial and lymphoepithelial lesions, 63% for plasma cell shift, and 24% for germinal centers. Although FS ≥1 showed the highest sensitivity for patients with pSS (82%), specificity was higher for the other three features (98%-100%). The presence of two or more (of four) histopathological features had almost comparable sensitivity to FS alone, but specificity increased with 12% to 100%. For fulfillment of American College of Rheumatology/EULAR criteria, specificity increased from 84% to 95% when an abnormal biopsy was defined by the presence of two or more histopathological features instead of FS ≥1 only. CONCLUSION: The diagnostic accuracy of the labial gland biopsy increases when other histopathological features besides FS are taken into account, by reducing the number of false-positive biopsies.

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.

Site-specific radiation dosage and implant survival in oral cancer patients: A cohort study.

OBJECTIVES: We assessed the radiation dosages (Dmean ) on implant regions to identify the threshold for implant loss in patients with an intraoral malignancy treated with dental implants to support a mandibular denture during ablative surgery before volumetric-modulated arc therapy (VMAT). MATERIALS AND METHODS: Data was collected prospectively from 28 patients treated surgically for an intraoral malignancy, followed by postoperative radiotherapy (VMAT) and analyzed retrospectively. Patients received 2 implants in the native mandible during ablative surgery. Implant-specific Dmean values were retrieved from the patients' files. Radiographic bone loss was measured 1 year after implant placement and during the last follow-up appointment. Implant survival was analyzed with the Kaplan-Meier method. Univariate logistic regression and Cox-regression analyses were performed to investigate the effect of increasing implant-specific radiation dosages on implant loss. RESULTS: Five out of 56 placed implants were lost during follow-up (median 36.0 months, IQR 39.0). Radiographically, peri-implant bone loss occurred in implants with a Dmean > 40 Gy. Implant loss occurred only in implants with a Dmean > 50 Gy. CONCLUSION: An implant-specific Dmean higher than 50 Gy is related to more peri-implant bone loss and, eventually, implant loss.

ITI consensus report on zygomatic implants: indications, evaluation of surgical techniques and long-term treatment outcomes.

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.

Immunohistological profiling confirms salivary gland-like nature of the tubarial glands and suggests closest resemblance to the palatal salivary glands.

BACKGROUND AND PURPOSE: High label uptake in 68 Ga-PSMA-11 PET/CT recently identified a bilateral nasopharyngeal structure as a salivary gland (SG)-like additional 'area of interest', to be considered in conditions affecting SGs. These structures were termed 'tubarial glands'. We aimed to further characterize their histological and immunohistochemical position compared to established SGs. METHODS: Tubarial gland tissue was compared with parotid, submandibular, sublingual, palatal and labial SGs tissue using immunohistological techniques. RESULTS: Expression of acinar cell-associated aquaporin-5 (AQP5) was detected in tubarial glands, in an apical location associated in control, established SGs with polarized, secretory acinar cells. Keratin14 (KRT14) expression in cells peripheral to AQP5+ clusters also suggested presence of myoepithelial cells. α-amylase, prolactin-induced protein, proline rich protein Haelll subfamily 2, and Muc5B expression suggests mucous acinar cell presence, and presence of muco-serous acinar cells peripheral to putative mucous acinar cells. Expression of adrenergic receptor-ß1 by acinar-like cells of the tubarial gland suggests ability to transduce sympathetic neuronal signaling. In terms of ductal architecture, tubarial glands contained large excretory-like ducts (similar to all other SGs), and squamous ducts, comprised of intermingled KRT14+ and KRT7+ cells. These squamous ducts were also observed in palatal, sublingual and labial SGs. No striated or intercalated ducts were observed, similar to palatal SGs. CONCLUSION: Based on histological and immunohistochemical analyses, the tubarial glands resemble SGs. They most convincingly echo characteristics of the palatal SGs in terms of ductal cells, and both the palatal and labial SGs when considering acinar cells.

Mortality risk factors in primary Sjögren syndrome: a real-world, retrospective, cohort study.

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.

FDG-PET/CT discriminates between patients with and without lymphomas in primary Sjögren's syndrome.

OBJECTIVES: To assess the usefulness of [18F]-fluorodeoxyglucose (FDG)-PET/CT (i) to discriminate between primary SS (pSS) patients with and without lymphomas and (ii) to evaluate systemic disease activity in pSS. METHODS: ACR-EULAR-positive pSS patients who underwent FDG-PET/CT were included. Scans were visually evaluated and quantitative analysis was performed by measuring standardized uptake values (SUV) of salivary and lacrimal glands and systemic regions. Receiver operating characteristic curve analyses were performed to find SUV cut-off values to discriminate between lymphoma and non-lymphoma. RESULTS: Of the 70 included patients, 26 were diagnosed with a pSS-associated lymphoma, mostly of the mucosa-associated lymphoid tissue type (23/26). Lymphoma patients showed higher FDG uptake in the parotid and submandibular glands, and more frequently showed presence of nodular lung lesions, compared with non-lymphoma patients. The accuracy of the maximum SUV (SUVmax) in the parotid and submandibular gland to predict lymphoma diagnosis was good, with optimal cut-off points of 3.1 and 2.9. After combining these three visual and quantitative findings (nodular lung lesions, parotid SUVmax > 3.1 and submandibular SUVmax > 2.9), sensitivity was 92% when at least one of the three features were present, and specificity was 91% in case at least two features were present. Furthermore, FDG-PET/CT was able to detect systemic manifestations in pSS patients, mostly involving lymph nodes, entheses and lungs. CONCLUSIONS: FDG-PET/CT can assist in excluding pSS-associated lymphomas in patients without PET abnormalities, possibly leading to a decrease of invasive biopsies in suspected lymphoma patients. Furthermore, FDG-PET/CT is able to detect systemic manifestations in pSS and can guide to the best biopsy location.

Effects of Upper Blepharoplasty Techniques on Headaches, Eyebrow Position, and Electromyographic Outcomes: A Randomized Controlled Trial.

The aim of this study was to assess changes in headaches, eyebrow height, and electromyographic (EMG) outcomes of the frontalis and orbicularis oculi muscles, after an upper blepharoplasty with or without resecting a strip of orbicularis oculi muscle. In a randomized controlled trial, 54 patients received an upper blepharoplasty involving either only removing skin (group A) or removing skin with an additional strip of orbicularis muscle (group B). Preoperative, and 6 and 12 months postoperative headache complaints were assessed using the HIT-6 scores and eyebrow heights were measured on standardised photographs. Surface EMG measurements, i.e., electrical activity and muscle fatigue, were assessed for the frontalis and orbicularis oculi muscles preoperatively and 2, 6, and 12 months postoperatively. Significantly fewer headaches were reported following a blepharoplasty. The eyebrow height had decreased, but did not differ between groups. Regarding the surface EMG measurements, only group A's frontalis muscle electrical activity had decreased significantly during maximal contraction 12 months after surgery (80 vs. 39 mV, p = 0.026). Fatigue of both the frontalis and the orbicularis oculi muscles did not change significantly postoperatively compared to baseline. EMG differences between groups were minor and clinically insignificant. The eyebrow height decreased and patients reported less headaches after upper blepharoplasty irrespective of the used technique.

Impact of medications on salivary flow rate in patients with xerostomia: a retrospective study by the Xeromeds Consortium.

OBJECTIVES: This study evaluates the impact of systemic medications and polypharmacy on unstimulated (UWS) and chewing-stimulated whole saliva (SWS) flow rates in patients with xerostomia. MATERIAL AND METHODS: This cross-sectional multicenter study is based on data of patients referred to five oral medicine outpatient practices in Europe and USA from January 2000 and April 2014. Relevant demographic, social, medical history and current medications were collected. RESULTS: The study included 1144 patients, 972 (85%) females, with a mean (SD) age of 59 (14.1) years. In unmatched patients, the UWS flow rate was lower in patients taking a medication (vs. not taking a medication) from the following drug categories: opioid analgesics, anticonvulsants, antidepressants, antihypertensives, benzodiazepines, corticosteroids, diuretics, disease-modifying antirheumatic drugs (DMARDs) and hormones. There was a greater negative effect on SWS flow rate in patients taking (vs. not taking) anticonvulsants, antidepressants, benzodiazepines, corticosteroids, and DMARDs. In matched patients, both UWS (0.22 vs. 0.19 ml/min; p = 0.03) and SWS (0.97 vs. 0.85 ml/min; p = .017) flow rates were higher in patients on non-opioid analgesics (vs. not taking). The UWS flow rate was lower in patients taking antidepressants (vs. not taking) (0.16 vs. 0.22 ml/min p = .002) and higher (and within normal range) in patients taking sex hormones (vs. not taking) (0.25 vs. 0.16 ml/min; p = .005). On the other hand, SWS was lower in patients taking corticosteroid (vs. not taking) (0.76 vs. 1.07 ml/min; p = .002), and in patients taking DMARDs (vs. not taking) (0.71 vs. 0.98 ml/min; p = .021). Finally, differences in medians of both UWS and SWS were statistically significant in patients taking 1 or more than 1 opioid analgesic (vs. not taking, p ≤ .0001 and p = .031, respectively), 1 or more than 1 anticonvulsants (vs. not taking, p = .008 and p = .007), 1 or more than 1 antidepressants (vs. not taking, p < .0001 for both), 1 or more than 1 DMARDs (vs. not taking, p = .042, and p = .003). CONCLUSIONS: A greater negative impact on UWS and SWS flow rates was seen in patients taking more than one medication from the same drug class. Intake of antidepressants, corticosteroids and DMARDs is associated with lower whole saliva flow rates. CLINICAL RELEVANCE: Salivary flow rate can be modified by some specific medications, mostly by polypharmacy.

Traditional versus Laterally Extended Upper Blepharoplasty Skin Excisions: Objective and Patient-Reported Outcomes.

BACKGROUND: Different skin excision shapes may result in different aesthetic outcomes after upper blepharoplasty. METHODS: Two skin-only excision shapes were evaluated objectively and subjectively in 28 matched patients with laterally extended skin excision (group A) or traditional elliptical skin excision (group B). The pretarsal show, lateral eyebrow height, amount of scarring (evaluated with the Patient and Observer Scar Assessment Scale), and patient-reported aesthetic results (evaluated using FACE-Q) were scored and compared at 6 and 12 months postoperatively. RESULTS: In both groups, pretarsal show improved significantly after blepharoplasty. The homogeneity of pretarsal show improved significantly in the lateral extension group (group A) together with slightly more pretarsal show (0.5 to 0.8 mm at central pupil region) at 6 and 12 months of follow-up compared with group B ( P = 0.004). A trend was observed in the exocanthion 45-degree measurement, in which group A had 0.6 mm greater pretarsal show 6 months postoperatively. Homogeneity of the pretarsal show had improved significantly in group A, but not in group B, at 12 months after blepharoplasty. No other significant differences were observed between the groups regarding pretarsal show measurements or FACE-Q scores. Both groups showed descent of the lateral eyebrow, but this was only significant in group B. Group B showed 1.4 to 2.0 mm more descent compared with group A. Scarring and adverse effects scores were low in both groups and did not differ. CONCLUSION: Laterally extended skin excision and traditional elliptical skin excision both result in positive aesthetic results, but the laterally extended skin excision technique is accompanied by a slightly more favorable outcome. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

The performance of two-implant overdentures in the atrophic maxilla: a case series with 1-year follow-up.

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.

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.

Influence of Oral Microbiota on the Presence of IgA Anti-Citrullinated Protein Antibodies in Gingival Crevicular Fluid.

Introduction: The 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. Aim: The 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 Methods: Healthy 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. Results: Between 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. Conclusion: Periodontitis and certain taxa, including Porphyromonas, seem to be associated with the local presence of ACPA in the periodontium.