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Objectives To compare focus score 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, and for CD3, CD20, CD45, cytokeratin, CD21, Bcl6, activation-induced deaminase (AID) and IgA/IgG. Focus score 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% (focus score) and 93% [(pre-)lymphoepithelial lesions (LELs)]. More labial gland biopsies had a focus score ≥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 fewer B-lymphocytes and germinal centres/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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: Temporomandibular joint (TMJ) osteoarthritis is a degenerative disease of the TMJ. It is characterized by progressive degradation of the extracellular matrix components of articular cartilage, with secondary inflammatory components leading to pain in the temporomandibular region and reduced mouth opening. Current treatments do not halt disease progression, hence the need for new therapies to reduce inflammation and, consequently, improve symptoms. The aim of our randomized controlled clinical trial protocol is to investigate the efficacy of adjuvant intra-articular injections of autologous tissue-like stromal vascular fraction (tSVF), compared to arthrocentesis alone, in reducing pain and improving mouth opening in TMJ osteoarthritis patients. Materials and Methods: The primary endpoint analysis will consist of the visual analogue scale (VAS) for pain. The secondary endpoint analyses will include maximal interincisal mouth opening measurements; assessment of oral health and mandibular function based on the oral health impact profile (OHIP) questionnaire and mandibular functional impairment questionnaire (MFIQ); complications during the follow up; synovial cytokine analysis at baseline and after 26 weeks; and nucleated cells and tSVF (immuno)histochemistry analyses of the intervention group. Discussion: Our randomized clinical trial protocol will be applied to evaluate the efficacy of a new promising tSVF injection therapy for TMJ osteoarthritis. The safety of intra-articular injections of tSVF has been proven for knee osteoarthritis. However, since a tSVF injection is considered a heterologous application of cell therapy, the regulatory requirements are strict, which makes medical ethical approval challenging. [ABSTRACT FROM AUTHOR]

Clinical indications for adipose tissue therapy are expanding towards a regenerative-based approach. Adipose-derived stromal vascular fraction consists of extracellular matrix and all nonadipocyte cells such as connective tissue cells including fibroblasts, adipose-derived stromal cells (ASCs) and vascular cells. Tissue stromal vascular fraction (tSVF) is obtained by mechanical fractionation, forcing adipose tissue through a device with one or more small hole(s) or cutting blades between syringes. The aim of this scoping review was to assess the efficacy of mechanical fractionation procedures to obtain tSVF. In addition, we provide an overview of the clinical, that is, therapeutic, efficacy of tSVF isolated by mechanical fraction on skin rejuvenation, wound healing and osteoarthritis. Procedures to obtain tissue stromal vascular fraction using mechanical fractionation and their associated validation data were included for comparison. For clinical outcome comparison, both animal and human studies that reported results after tSVF injection were included. We categorized mechanical fractionation procedures into filtration (n = 4), centrifugation (n = 8), both filtration and centrifugation (n = 3) and other methods (n = 3). In total, 1465 patients and 410 animals were described in the included clinical studies. tSVF seems to have a more positive clinical outcome in diseases with a high proinflammatory character such as osteoarthritis or (disturbed) wound healing, in comparison with skin rejuvenation of aging skin. Isolation of tSVF is obtained by disruption of adipocytes and therefore volume is reduced. Procedures consisting of centrifugation prior to mechanical fractionation seem to be most effective in volume reduction and thus isolation of tSVF. tSVF injection seems to be especially beneficial in clinical applications such as osteoarthritis or wound healing. Clinical application of tSVF appeared to be independent of the preparation procedure, which indicates that current methods are highly versatile. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective Salivary glands of primary SS (pSS) patients characteristically harbour periductal infiltrates, in which lymphoepithelial lesions (LELs) can develop. LELs are composed of hyperplastic ductal epithelium with infiltrating lymphocytes and may assist in the challenging diagnostic process of pSS. As manual identification of LELs remains difficult, we aimed to identify LELs by using an objective digital image analysis (DIA) algorithm that detects intraepithelial lymphocytes. Methods A virtual triple-staining technique developed for this study was used to count intraepithelial lymphocytes in consecutive slides stained for CD3 (T-lymphocytes), high-molecular-weight cytokeratin (hmwCK) (striated ducts) and CD20 (B-lymphocytes) in labial and parotid gland biopsies in a diagnostic cohort of 109 sicca patients. Patients were classified as having pSS or non-SS according to the ACR-EULAR classification criteria. Results T-lymphocytes were detected in almost all analysed ducts of pSS and non-SS sicca patients, whereas intraepithelial B-lymphocytes were present in 59–68% of labial and parotid gland biopsies of pSS patients, against only 2–3% of patients classified as non-SS. Intraepithelial B-lymphocytes were found in almost all striated ducts with hyperplasia (LELs). Remarkably, ∼25% of analysed striated ducts without hyperplasia of pSS patients also contained B-lymphocytes (precursor-LELs). Furthermore, presence of intraepithelial B-lymphocytes was associated with clinical parameters of pSS (i.e. serology). Conclusion The presence of intraepithelial B-lymphocytes in salivary gland biopsies of sicca patients is a clear indicator of pSS and can be used as an objective alternative to LEL scoring. Therefore, identification of B-lymphocyte–containing ducts should be added to the diagnostic histopathological work-up of patients suspected of pSS. [ABSTRACT FROM AUTHOR]

Objective The involvement of salivary glands in primary SS (pSS) can be assessed in different ways: histopathology, salivary flow and ultrasonography. To understand the relative value of these different approaches, it is crucial to understand the relationship between them. As we routinely perform these three modalities in the parotid gland for disease evaluation, our aim was to investigate the construct validity between these modalities in one and the same gland. Methods Consecutive sicca patients underwent a multidisciplinary diagnostic workup including parotid gland biopsy, collection of parotid gland–specific saliva and parotid gland ultrasonography. Patients who were classified as pSS according to the ACR-EULAR criteria were included. Construct validity was assessed using Spearman's correlation coefficients. Results The 41 included pSS patients completed a full workup within a mean time interval of 2.6 months. Correlations between histopathological features and stimulated parotid salivary flow were fair (ρ  = −0.123 for focus score and ρ  = −0.259 for percentage of CD45+ infiltrate). Likewise, poor correlations were observed between stimulated parotid salivary flow and parotid ultrasonography (ρ  = −0.196). Moderate to good associations were found between the histopathological items focus score and the percentage of CD45+ infiltrate, with parotid US scores (total US score: ρ  = 0.510 and ρ  = 0.560; highest for homogeneity: ρ  = 0.574 and ρ  = 0.633). Conclusion Although pSS-associated ultrasonographic findings did correlate with histopathological features, the three modalities that evaluate salivary gland involvement assess different (or at best partly related) constructs. Therefore histopathology, salivary flow and ultrasonography are complementary measurements and cannot directly replace each other in the workup of pSS. [ABSTRACT FROM AUTHOR]