The Novel OMERACT Ultrasound Scoring System for Salivary Gland Changes in Patients With Sjögren Syndrome Is Associated With MRI and Salivary Flow Rates.

OBJECTIVE: To assess the construct validity of the novel Outcome Measures in Rheumatology (OMERACT) ultrasound (US) semiquantitative scoring system for morphological lesions in major salivary glands by comparing it with magnetic resonance imaging (MRI) and unstimulated whole salivary flow rates (U-WSFRs) in patients with primary Sjögren syndrome (pSS). METHODS: Nine sonographers applied the OMERACT 0-3 grayscale scoring system for parotid (PGs) and submandibular glands (SMGs) in 11 patients with pSS who also had MRIs performed. These were evaluated by 2 radiologists using a semiquantitative 0-3 scoring system for morphological lesions. The agreement between US and MRI and the association between U-WSFRs and imaging structural lesions was determined. A score ≥ 2 for both US and MRI was defined as gland pathology. RESULTS: The prevalence of US morphological lesions in 11 patients with a score ≥ 2 was 58% for PGs and 76% for SMGs, and 46% and 41% for PGs and SMGs, respectively, for MRI. The agreement between OMERACT US scores and MRI scores was 73-91% (median 82%) in the right PG and 73-91% (median 91%) in the left PG, 55-91% (median 55%) in the right SMG and 55-82% (median 55%) in the left SMG. When relations between the presence of hyposalivation and an US score ≥ 2 were examined, agreement was 91-100% (median 83%) in both PGs and 55-91% (median 67%) in both SMGs. CONCLUSION: There is moderate to strong agreement between the OMERACT US and MRI scores for major salivary glands in patients with pSS. Similar agreement ratios were observed between the higher OMERACT US scores and presence of hyposalivation.

Psychological resilience in patients with primary Sjögren's syndrome: effect of involvement of major salivary and lacrimal glands.

The aim of this study was to assess whether the involvement of major salivary and lacrimal glands in primary Sjögren's syndrome (pSS) affected the psychological resilience of patients. This cross-sectional study included 116 patients with pSS. Data were collected through clinical examinations, measurement of salivary flow rates (SFRs), and from Schirmer's test, as well as from patient-reported outcome measures (PROMs), such as the European League Against Rheumatism (EULAR) Sjögren's Syndrome Patient Reported Index (ESSPRI), Brief Resilience Scale (BRS), Work Productivity and Activity Impairment (WPAI), Oral Health Impact Profile-14 (OHIP-14), and the Hospital Anxiety and Depression Scale (HADS). Hyposalivation was defined as an unstimulated SFR of ≤0.1 mL/min. The BRS score (mean ± SD = 2.60 ± 0.69) was lower in patients with recurrent parotitis (2.11 ± 0.37) than in those without recurrent parotitis (2.67 ± 0.86), in the whole group. In patients with an unacceptable symptom state (ESSPRI score ≥ 5 points), a lower BRS score was observed in patients with both hyposalivation and ocular dryness (2.59 ± 0.69) than in patients with isolated hyposalivation (2.84 ± 0.84). The BRS score was also negatively associated with the WPAI-Daily Impairment and OHIP-14 scores in patients with hyposalivation as well as with HADS-A (the seven items of HADS relating to the anxiety dimension) and HADS-D (the seven items of HADS relating to the depression dimension) in the whole group. The results suggest that psychological resilience in pSS may be affected by recurrent parotitis, the levels of anxiety and depression, as well as hyposalivation with ocular dryness.

Treat to target in Behcet's disease: Should we follow the paradigm of other systemic rheumatic diseases?

During the last decades the efficacy of biologic agents, mainly of anti-TNFs, in controlling the activity of serious manifestations of Behcet's Disease (BD) has been established. On the other hand, the clinical heterogeneity of BD has precluded the validation of a widely-accepted composite index for disease assessment and for target disease-state definitions, such as low disease activity and remission, and the testing of their implementation in clinical practice. Therefore, in contrast to other systemic rheumatic diseases, a treat-to-target strategy has not yet been developed in BD. There are several challenges towards this approach, including standardization of outcome measures for assessing the disease activity in each-affected organ and construction of a composite disease activity index. The challenges for the development of a treat-to-target strategy and possible solutions are discussed in this position paper, which stemmed from a round table discussion that took place in the 19th International Conference on BD.

The impact of the COVID-19 pandemic on patients with Behçet's syndrome within the framework of Maslow's hierarchy of needs: implications for patient empowerment in national or global emergencies.

OBJECTIVES: The aim of this online survey was to assess the impact of the COVID-19 pandemic on patients with Behçet's syndrome (BS) using Maslow's hierarchy of needs. METHODS: Sixty-eight BS patients from the UK completed an online questionnaire that covered three components of Maslow's hierarchy of needs regarding Physiological needs (sleep, food, mobility), Safety needs (employment, health), Social needs (relationships), personal precautions and main concerns regarding COVID-19. RESULTS: The patients received a letter from the NHS (66.2%) advising shielding. Health concerns were addressed using Tele-medicine by telephone consultations and e-mails to access BS specialists during lockdown (44.1%; 27.9%). In addition, patients also obtained information through official government and Behçet corporate health web pages related to Behçet's disease for self-empowerment. During lockdown, their weekly working hours were reduced (26.65±13.86 vs. 20.79±17.94) (p=0.017) and the employment rate was decreased (32.6% vs. 26.7%) in comparison to pre-lockdown. Moreover, the reduction in frequency of exercise per week (4.39±1.94 vs. 3.71±2.26) and healthy food consumption (73.5 % vs. 47.1%) per week were also reported (p=0.007; p=0.001, respectively). Furthermore, patients experienced sleeping less (54.4%) and feeling lonely (66.1%). CONCLUSIONS: Using Maslow's hierarchy of needs provided a framework for reviewing the quality of basic needs in patients' life during lockdown. These needs are required for healthy social lives and the deprivation should be considered while considering healthcare planning. Since lockdown appeared to have a negative influence on patients' lives and disease management in the framework of patient-centred, the empowerment of patients gained importance at this point.

Does decision tree analysis predict oral ulcer activity-related factors in patients with Behçet's syndrome?

OBJECTIVES: The study aimed to identify the interactions among treatment protocols and oral ulcer activity related factors in patients with Behçet's syndrome (BS) using the Classification and Regression Tree (CART) algorithm. METHODS: In this cross-sectional study, 979 patients with BS were included from16 centres in Turkey, Jordan, Brazil and the United Kingdom. In the CART algorithm, activities of oral ulcer (active vs. inactive), genital ulcer (active vs. inactive), cutaneous involvement (active vs. inactive), musculoskeletal involvement (active vs. inactive), gender (male vs. female), disease severity (mucocutaneous and musculoskeletal involvement vs. major organ involvement), smoking habits (current smoker vs. non-smoker), tooth brushing habits (irregular vs. regular), were input variables. The treatment protocols regarding immunosuppressive (IS) or non-IS medications were the target variable used to split from parent nodes to purer child nodes in the study. RESULTS: In mucocutaneous and musculoskeletal involvement (n=538), the ratio of IS use was higher in patients with irregular toothbrushing (ITB) habits (27.1%) than in patients with regular toothbrushing (RTB) habits (14.2%) in oral ulcer activity. In major organ involvement (n=441), male patients with ITB habits were more likely treated with IS medications compared to those with RTB habits (91.6% vs. 77.6%, respectively). CONCLUSIONS: Male BS patients on IS who have major organ involvement and oral ulcer activity with mucocutaneous and musculoskeletal involvement have irregular toothbrushing habits. Improved oral hygiene practices should be considered to be an integral part for implementing patient empowerment strategies for BS.

A cross-sectional study on activity impairment in primary Sjogren's syndrome.

OBJECTIVE: The aim of this cross-sectional study was to show relations between activity impairment and salivary gland involvement for patient empowerment in primary Sjogren's syndrome (pSS). METHODS: In the study, 86 patients with pSS were included. The data were collected through clinical examinations and a questionnaire regarding Work Productivity and Activity Impairment (WPAI), EULAR Sjogren's syndrome patient-reported index (ESSPRI) and Oral Health Impact Profile-14 (OHIP-14). Relations were analysed by using mediation and moderation analyses. In simple mediation analysis, an independent variable (X) influences outcome variable (Y) through a mediator variable (M) whereas a moderator variable (W) affects the direction of the relationship between the dependent (Y) and independent variables (X). RESULTS: Increases in ESSPRI-Dryness score (X) (p = 0.0189) and OHIP-14 score (M) (p = 0.0004) were associated with the poor WPAI activity impairment score (Y) in the first mediation analysis. The WPAI activity impairment score was mediated by the elevated ESSPRI-Fatigue score (X) (p = 0.03641) and low U-SFR (M) (p = 0.0000) in the second mediation analysis. In addition, ESSPRI-Pain score (W) was the significant moderator for WPAI activity impairment (Y) in patients without hyposalivation in the moderation analysis (p = 0.0010). CONCLUSION: WPAI activity impairment was affected by both ESSPRI-Dryness with OHRQoL and ESSPRI-Fatigue with SFR in glandular involvement.

The assessment of presenteeism and activity impairment in Behçet's syndrome and recurrent aphthous stomatitis: a multicentre study.

OBJECTIVE: To evaluate key factors for presenteeism and activity impairment in multinational patients with Behçet's syndrome (BS) and recurrent aphthous stomatitis (RAS). METHODS: In this cross-sectional study, 364 BS patients from Jordan, Brazil, the United Kingdom and Turkey and 143 RAS patients from the United Kingdom and Turkey were included. The Work Productivity Activity Impairment (WPAI) scale was used for presenteeism and activity impairment. Mediation analyses were performed to evaluate both direct and indirect causal effects. RESULTS: Presenteeism score was higher in active patients with genital ulcers and eye involvement as well as patients with comorbidities and current smokers than the others in BS (P < 0.05). In RAS, presenteeism score was elevated by oral ulcer activity in the direct path (P = 0.0073) and long disease duration as a mediator in the indirect path (P = 0.0191). Patients with active joint involvement had poor scores in absenteeism, presenteeism, overall impairment and activity impairment compared with those of inactive patients (P < 0.05). Using mediation analysis, the activity impairment score was directly mediated by joint activity (P = 0.0001) and indirectly mediated through oral ulcer-related pain in BS (P = 0.0309). CONCLUSION: In BS, presenteeism was associated with disease activity, presence of comorbidities and being a current smoker, whereas in RAS, presenteeism was associated with oral ulcer activity and increased length of the disease. Moreover, activity impairment was adversely affected by joint activity and oral ulcer related pain in BS. Patients need to be empowered by using appropriate treatment strategies in their working environment and daily life.

Femoral vein wall thickness measurement: A new diagnostic tool for Behçet's disease.

OBJECTIVES: Diagnosing Behçet's disease (BD) is a challenge, especially in countries with a low prevalence. Recently, venous wall thickness (VWT) in lower extremities has been shown to be increased in BD patients. In this study, we aimed to investigate the diagnostic performance of common femoral vein (CFV) thickness measurement in BD and whether it can be used as a diagnostic tool. METHODS: . Patients with BD (n = 152), ankylosing spondylitis (n = 27), systemic vasculitides (n = 23), venous insufficiency (n = 29), antiphospholipid syndrome (APS; n = 43), deep vein thrombosis due to non-inflammatory causes (n = 25) and healthy controls (n = 51) were included in the study. Bilateral CFV thickness was measured with ultrasonography by a radiologist blinded to cases. RESULTS: Bilateral CFV thickness was significantly increased in BD compared with all control groups (P < 0.001 for all). The area under the receiver operating characteristic curve for bilateral CFV thicknesses in all comparator groups was >0.95 for the cut-off value (0.5 mm). This cut-off value also performed well against all control groups with sensitivity rates >90%. The specificity rate was also >80% in all comparator groups except APS (positive predictive value: 79.2-76.5%, negative predictive value: 92-91.8% for right and left CFV, respectively). CONCLUSION: Increased CFV thickness is a distinctive feature of BD and is rarely present in healthy and diseased controls, except APS. Our results suggest that CFV thickness measurement with ultrasonography, a non-invasive radiological modality, can be a diagnostic tool for BD with sensitivity and the specificity rates higher than 80% for the cut-off value ≥0.5 mm.

Decreasing incidence and severity of Behçet's disease: a changing trend in epidemiological spectrum possibly associated with oral health

Behçet's disease (BD) is a systemic and inflammatory disorder that is mainly present along the ancient Silk Road, from the Mediterranean Sea to East Asia. A wide range of prevalence figures (0.1­420/100,000) have been reported for BD, also among Turkish populations of similar genetic background living in different countries. Recently, a decline in the incidence of BD and a change of the disease spectrum to less-severe manifestations have been reported from Japan and Korea, two genetically homogenous, affluent populations with limited immigration. It was hypothesized that a decline in infectious diseases, especially dental/periodontal infections, associated with the improvement in oral health, could be a part of these changes in the disease expression. Further epidemiological studies in other populations might demonstrate whether there is a worldwide similar trend and may provide a better understanding of the triggering factors for the onset and course of BD.

Evaluation of salivary gland ultrasonography in primary Sjögren's syndrome: does it reflect clinical activity and outcome of the disease?

OBJECTIVES: To evaluate associations between salivary gland ultrasonography (SGUS) and clinical characteristics, disease activity and outcome in patients with primary Sjögren's syndrome (pSS). METHODS: The parotid and submandibular salivary glands were examined by ultrasonography using two different scoring systems proposed by Hocevar et al. and Milic et al. on 85 pSS patients. Patients with inhomogeneity/hypoechoic areas with scores ≥2 in parotid and submandibular glands were classified as severe parotid or severe submandibular involvements, respectively. Disease activity and patient-reported severity were evaluated using the European League Against Rheumatism Sjögren's Disease Activity Index (ESSDAI) and the European League Against Rheumatism Sjögren's Patient Reported Index (ESSPRI). Salivary gland functional capacity was investigated by unstimulated whole saliva flow rate (U-WSFR). RESULTS: Of the activity scores, ESSPRI dryness component was higher in pSS patients who had scores above the cut-off values for Hocevar (6.1±2.3 vs. 4.9±2.6, p=0.026). The patients with any type of systemic involvement more frequently showed higher SGUS scores, according to both Hocevar (72.4 vs. 44.6%, p=0.013) and Milic (75.9 vs. 51.8%, p=0.026). These patients also showed a higher percentage of severe parotid/submandibular changes on US imaging (65.5 vs. 33.9%, p=0.005 and 75.9 vs. 51.8%, p=0.026 respectively). Higher SGUS scores according to cut-off values of both scoring systems and severe parotid/submandibular involvements were associated with both anti-Ro or double anti-Ro/La autoantibodies and inversely associated with U-WSFR. CONCLUSIONS: SGUS may be a useful imaging modality for the selection of patients with more severe disease status or who may require a tight follow-up schedule.

Oral ulcer activity assessment with the composite index according to different treatment modalities in Behçet's syndrome: a multicentre study.

OBJECTIVES: The aim of this multicentre study was to understand patients' needs and to evaluate the oral ulcer activity with the Composite Index (CI), according to different treatment modalities in Behçet's syndrome (BS). METHODS: BS patients (n=834) from 12 centres participated in this cross-sectional study. Oral ulcer activity (active vs. inactive) and the CI (0: inactive vs. 1-10 points: active) were evaluated during the previous month. The effects of treatment protocols [non-immunosuppressive: non-IS vs. immunosuppressive: (ISs)], severity (mild vs. severe), disease duration (<5 years vs. ≥5 years) and smoking pattern (non-smoker vs. current smoker) were analysed for oral ulcer activity. RESULTS: Oral ulcer activity was observed in 65.1% of the group (n=543). In both genders, the activity was higher in mild disease course with non-IS treatment group compared to severe course with ISs (p<0.05). As a resistant group, patients with mild disease course whose mucocutaneous symptoms were unresponsive to non-IS medications were treated with ISs in a limited period and achieved the highest CI scores in females. Oral ulcer activity and poor CI score were associated with disease duration less than 5 years compared to others in male patients (p<0.05). CONCLUSIONS: Oral ulcer activity pattern is affected by both the combination of disease course, treatment protocols and disease duration. CI scores reflected the oral clinical activity and CI might be a candidate scale to evaluate the efficacy of treatments during the follow-up of oral ulcer activity in BS.

Oral health is a mediator for disease severity in patients with Behçet's disease: A multiple mediation analysis study.

OBJECTIVES: The aim of the study was to examine whether oral health as an infection focus could mediate disease course in patients with Behçet's disease (BD). METHODS: In the study, oral health of 194 BD patients was examined at baseline and follow-up periods. The reasons for last dental visits were recorded as tooth extraction or regular control visits/planned treatments at the end of follow-up period. The Behçet's disease severity score was calculated with higher scores indicating a more severe course. Mediation analysis was carried out to assess the effects of oral health on disease severity score at follow-up period in the study. RESULTS: Dental and periodontal indices were found to be higher at follow-up visit compared to those of baseline (P < 0.05). Disease severity score was found to be higher in males (5.3 ± 2.4) compared to females (4.4 ±2.5) in the whole group (P = 0.005). Moreover, patients having tooth extraction at their last dental visit and patients with dental caries had a more severe disease course (5.4 ± 2.4; 5.5 ± 2.5) compared to others (4.2 ± 2.3; 4.4 ± 2.4; P < 0.0001). In multiple mediation analysis, disease severity score was a dependent variable and was directly mediated by male gender (B = -0.8822, P = 0.0145) and indirectly mediated through the presence of dental caries (B = 0.9509 P = 0.0110) and need of tooth extraction (B = 0.8758, P = 0.0128). CONCLUSION: Both presence of dental caries and need of tooth extraction were observed to be effective mediators for a more severe disease course in BD. Therefore, better oral health should be aimed to eliminate microbial factors, which are a part of pathogenic processes.

Health-related outcomes of importance to patients with Takayasu's arteritis.

OBJECTIVES: The need to include patients' perspectives as key outcomes in clinical trials is widely accepted. No disease-specific patient-reported outcomes have been developed in Takayasu's arteritis. This project was designed to identify outcomes of importance to patients with Takayasu's arteritis during active disease and remission across 2 different cultures. METHODS: Patients with Takayasu's arteritis from the US and Turkey were recruited to participate in semi-structured, one-on-one interviews or focus groups. The interviews and group sessions were recorded, transcribed, and entered into an Nvivo database. A line-by-line review of narrative data was used to develop themes describing the impact of Takayasu's arteritis on patients' life. US Patients were invited to freelist terms that they associated with disease states (active disease and remission). The Smith's Salience Index (SSI) was used to identify the most salient terms. RESULTS: Results. A total of 31 patients with Takayasu's arteritis participated in this study. Interviews and focus groups identified pain, fatigue, and emotional impact as common themes. Outcomes did not differ between the 2 countries. The most salient terms identified through freelisting were pain/discomfort and fatigue/low energy levels (SSI=0.56 and 0.33, respectively) during active disease and pain/discomfort and emotional impact (SSI=0.51 and 0.37, respectively) during remission. CONCLUSIONS: Patients with Takayasu's arteritis report a range of disease-specific symptoms across different cultures and disease states that are generally not specifically captured by generic patient-reported outcome tools currently used in research. Identifying disease-specific outcomes would advance clinical trials methodology to best capture the full spectrum of disease activity in Takayasu's arteritis.

Could Sublingual Immunotherapy Affect Oral Health in Children with Asthma and/or Allergic Rhinitis Sensitized to House Dust Mite?

BACKGROUND: Sublingual immunotherapy (SLIT) has been successfully employed in IgE-mediated respiratory allergies. However, it is not known whether the modulation of immune responses in the sublingual area during SLIT has any deleterious effect on oral health. We sought to determine the oral health prospectively in children receiving SLIT for house dust mite allergy. MATERIAL AND METHODS: Eighteen children with allergic asthma and/or rhinitis and 31 age-matched healthy controls (HC) were included in an open-labeled trial. Oral health was evaluated by scoring the decayed, missing, and filled teeth for primary (dmft) and permanent (DMFT) dentition, and the plaque and gingival indices. Moreover, cariogenic food intake and teeth-brushing habits were also noted at baseline and at 19 months. RESULTS: The mean age of the SLIT participants was 9.5 ± 3.1 years and that of the HC was 9.2 ± 3.7 years. The mean duration of SLIT was 19.13 ± 3.81 months. At baseline, the total dmft and DMFT indices were similar in the SLIT and HC groups (p > 0.05), which demonstrated poor hygiene overall. In the within-group comparisons at the examination at 19 months, the SLIT group had a lower number of carious primary teeth and a higher number of filled primary teeth compared to the count at baseline (p = 0.027 and p = 0.058, respectively). CONCLUSION: Our study showed no detrimental effect of SLIT on oral health during a period of 19 months of follow-up. Parents should be motivated to use dental health services to prevent new caries formation since our cohort had overall poor oral hygiene at the baseline.

Th17-Inducing Conditions Lead to in vitro Activation of Both Th17 and Th1 Responses in Behcet's Disease.

OBJECTIVES: Interleukin-17 (IL-17) has been associated with the pathogenesis of various autoimmune/inflammatory diseases. The aim of this study was to investigate the expression of Th17-related immunity in an innate immunity-dominated vasculitis, namely Behcet's disease (BD). METHODS: Peripheral blood mononuclear cells from 37 patients (age: 38.5 ± 9.8 years) with BD, and 25 healthy controls (HC) (age: 39.1 ± 9.3 years), were cultured in Th17-inducing conditions (IL-6, Phytohemagglutinin (PHA), IL-1ß, and IL-23) for 6 days. Cultured cells were stained with CD4, CD8, CD3, TCR gamma/delta, CD19, interferon-γ (IFN-γ), and IL-17 antibodies to determine the intracellular cytokine secretion by flow cytometry. RESULTS: IL-17 expression by CD8+ and γδ+ T cells was higher in BD compared to HC (p = 0.004, p = 0.003, respectively). No differences were observed between the groups in the IL-17 production by B cells. Under Th17-inducing conditions, production of IFN-γ by CD4+, CD8+, and γδ+ T cells was also higher in BD compared to HC (p < 0.05 in all). CONCLUSION: Our results suggest that under Th17-stimulating conditions, T cells express both IL-17 and IFN-γ in BD. More prominent IL-17 and IFN-γ production by all lymphocyte subsets in BD might be associated with the increased innate responses, early tissue neutrophil infiltrations and late adaptive immunity in BD.

Sequencing of 16S rRNA reveals a distinct salivary microbiome signature in Behçet's disease.

Behçet's disease (BD) is characterized by recurrent oro-genital ulcers, mucocutaneous lesions, and serious organ involvement. We investigated the salivary microbiome in BD using high-throughput sequencing of the 16S rRNA V4 region. Stimulated saliva samples were collected from 31 BD patients and 15 healthy controls, and in 9 BD patients, a second saliva sample was collected following dental and periodontal treatment. Sequence analysis identified a total of 908 operational taxonomic units (OTUs) present across all samples. Patients had a microbial community structure that is significantly less diverse than healthy controls. The most overabundant species in BD was Haemophilus parainfluenzae, while the most depleted included Alloprevotella rava and species in the genus Leptotrichia. Periodontal treatment improved oral health indices in BD but had no short-term effect on bacterial community structure. Neither the BD-associated genetic risk locus within the HLA-B/MICA region nor being on immunosuppressive medications explained the differences between patients and controls.

A new Mucocutaneous Activity Index for Behçet's disease.

OBJECTIVES: Patient-reported outcomes are increasingly accepted to be major domains in chronic disorders. The aim of this study was to develop a patient-derived disease activity index in Beh-çet's disease (BD). METHODS: One hundred and seventy-seven BD patients (M/F: 69/108) were included in the study. Data were collected by clinical examination and a questionnaire regarding a Mucocutaneous Index (MI) with genital ulcer activity (GI), erythema nodosum activity (EI) and the composite index (CI) for oral ulcers, as subscales of it. Self-reported treatment evaluation was carried out as criterion validity. Patients whose symptoms completely disappeared or decreased significantly, were categorised as 'improved group', others were classified as 'non-improved group'. RESULTS: Among the study group, 79.7% of the patients (n=141) were active, whereas 20.3% were inactive (n=36). Scores of CI, GI, EI and MI score were 0±0 in inactive ones, whereas scores were 5.65±2.36 for CI, 0.81±2.34 for GI, 0.91±2.35 for EI and 6.25±5.1 for MI in actives (p=0.000 for all). MI score was significantly higher in 'non-improved group' (65.5%) compared to 'improved group' (34.5%) (p<0.0001). CONCLUSIONS: The mucocutaneous activity index may help decision-making process for treatment strategies in BD patients.

Investigation of Predisposing Risk Factors in Adolescent Male Water Polo Players.

BACKGROUND: Shoulder injuries are prevalent in adolescent water polo (WP) players. Study aimed to determine whether preseason shoulder characteristics (range of motion [ROM], flexibility, and strength) and core endurance can identify athletes at risk of future shoulder injuries. HYPOTHESIS: Shoulder characteristics, including changes in ROM (internal rotation [IR], external rotation [ER], and total), strength (IR and ER), pectoralis minor flexibility, shoulder capsule flexibility, and core endurance, would be risk factors for shoulder reinjury in athletes with previous overuse injuries compared with noninjured athletes. STUDY DESIGN: Prospective cohort study. LEVEL OF EVIDENCE: Level 3. METHODS: At baseline, 53 male youth WP players (mean age, 16.6 ± 3.5 years) were assigned to Group 1 (with previous shoulder injuries [G1, n = 26]) and Group 2 (without previous shoulder injuries [G2, n = 27]). ROM, flexibility, strength, and core muscle endurance were assessed preseason. After a 12-month follow-up, players were again divided into those who developed new shoulder injuries (G3, n = 27) and those who remained healthy (G4, n = 26). RESULTS: Total of 26 players (49%) had previous shoulder injuries at baseline. At baseline, decreased pectoralis minor flexibility, IR, total ROM, and core endurance were found in players with a previous shoulder injury compared with players without a previous shoulder injury (P < 0.05). CONCLUSION: At baseline, a significant difference was present in proposed risk factors (shoulder and core endurance parameters) between players with and without a previous shoulder injury. Shoulder IR ROM and years of experience were significant predictors of shoulder injury. Early detection of modifiable proposed risk factors may help prevent reinjury in young athletes. CLINICAL RELEVANCE: Screening at an early age can help identify and address pre-existing injuries, support youth athletes' return to sport after a shoulder injury, prevent new injuries, and improve performance.

Pro-inflammatory cytokine and caspase-1 responses to pattern recognition receptor activation of neutrophils and dendritic cells in Behcet's disease.

OBJECTIVE: Activated innate immunity is implicated in the pathogenesis of Behcet's disease (BD). To clarify the mechanisms of innate immune responses, we investigated inflammasome activation in dendritic cells (DCs) and neutrophils, following stimulation with two different pattern recognition receptors (PRRs) RIG-1-like (RLR) and NOD-like (NLR) in patients with BD. METHODS: Sixteen active BD patients with mucocutaneous lesions and 17 healthy controls (HCs) were included in this study. DCs were generated from monocytes. DCs and isolated neutrophils were activated by RLR and NLR ligands. Caspase-1 activation and expression of p38 and RIP2 were determined by flow cytometry. Levels of IL-1ß, IL-6, TNF-α, IFN-α and IL-18 in culture supernatants were measured by ELISA. RESULTS: Activation of caspase-1 following intracellular PRR stimulation was found to be of similar levels in DCs and neutrophils of BD patients compared with HCs. However, activation of DCs from BD patients to NOD2 stimulus measured by the expression of RIP2 and p38 as well as IL-18 levels was found to be slightly defective (P < 0.05). In neutrophil cultures, IL-6 levels were lower in response to all stimuli in patients with BD compared with HCs (P < 0.01). CONCLUSION: Inflammasome formation following stimulation with NOD1/NOD2 and RIG measured by caspase-1 activation, cytokine levels and expression of RIP2 and p38 seems to be functionally normal in DCs and neutrophils of BD patients, although slightly defective responses in some pathways and cytokine levels were observed. These results may suggest that caspase-1-independent pathways such as toll-like receptors may be more prominent in BD pathogenesis.