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ObjectivesPsoriasis and psoriatic arthritis (PsA) are independently associated with comorbidities, including obesity and metabolic syndrome, which may impact treatment outcomes. This study aimed to assess baseline differences between patients with plaque psoriasis alone and those with concomitant PsA, and to investigate the impact of these characteristics on ustekinumab (UST) persistence and outcomes.Methods9057 patients receiving UST or conventional systemic disease-modifying antirheumatic drugs were selected from the British Association of Dermatologists Biologic and Immunomodulators Register. The psoriasis and PsA cohorts were compared at baseline. Time to discontinuation during 10-year follow-up was assessed using multivariable Cox regression and Kaplan–Meier analyses, stratifying for interacting covariates and PsA status. Generalised linear mixed models assessed the impact of baseline characteristics on Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index over time.ResultsGreater comorbidity burden, including hypertension, diabetes, obesity and depression, and greater inability to work were observed in the PsA cohort than in the psoriasis cohort. PsA (HR 1.98), female sex (HR for male sex 0.72) and depression (HR 1.21) were associated with shorter UST persistence. PsA showed a differential association with UST persistence by PASI strata and prior biologic exposure. Quality of life was negatively impacted by depression and PsA.ConclusionsThe negative impact of comorbidities on treatment persistence identified in this study emphasises the need for patient-centric, multidisciplinary care in screening for and managing comorbidities in psoriasis and PsA treatment. Psychological support and lifestyle management of modifiable risk factors, including obesity, should be considered.

Background/Aims Treatment guidelines for psoriatic arthritis consider both skin and joint involvement and recommend collaborative multidisciplinary team (MDT) working when selecting therapy. However, multidisciplinary practice for psoriatic disease (PD) has not been well studied, with little data on service models and current practice. This survey explored collaborative working in PD treatment by rheumatology and dermatology healthcare professionals (HCPs) to provide a better understanding of current working patterns, collaborating specialties, as well as benefits and challenges of combined clinics for PD management. Methods An online survey was emailed to rheumatology and dermatology HCPs using professional networks. We requested information on role, collaborating specialties, benefits and barriers to collaborative working in PD, and the impact of COVID-19. The ideal service model and additional comments completed the survey. Results We received 80 responses between October 2020 and April 2021, covering England, Wales, Scotland and Northern Ireland. Of these, 56 respondents (70.0%) were consultants, 22 (27.5%) clinical nurse specialists and one each a lead pharmacist (1.3%) and specialist registrar (1.3%). Rheumatology HCPs accounted for 40.0% of respondents (n = 32) and dermatology HCPs for 60.0% (n = 48). As part of their PD MDT, most respondents (n = 60, 75.0%) worked collaboratively with other specialties. Combined clinics, whether virtual, face to face or an MDT, accounted for 51.5% of collaborative working for rheumatology HCPs and 58.9% for dermatology HCPs. Collaboration with other specialists mainly occurred by email or written referrals (Table 1). The most important perceived benefits of combined clinics were shared knowledge, better patient outcomes and patient satisfaction. The biggest challenges to setting up combined clinics were job plan time (rated as ‘difficult’ or ‘very difficult’ by 78.8% of respondents), logistics (67.5%) and unsupportive senior management (66.3%), while 77.5% felt COVID-19 had partial or significant impact on combined clinics. Conclusion This is the first survey to explore UK collaborative working in PD. Approaches varied, with different models of working and little consistency. While HCPs appreciated the benefits of collaborative working, numerous challenges in establishing formal arrangements were identified. More evidence is needed to demonstrate the perceived benefits of collaborative working in improving patient outcomes by standardising best practice. Disclosure A. Kaul: Consultancies; AK has received payment for advisory boards from AbbVie, Janssen, Leo, MSD, Novartis and Pfizer. Honoraria; AK has received speaker fees from AbbVie, Eli Lilly, Janssen, Leo, MSD, Novartis and Pfizer. L. Savage: Consultancies; LS has received payment for advisory boards from AbbVie, Almirall, Biogen, Eli Lilly, Galderma, Janssen-Cilag, Leo, Novartis, Pfizer and UCB. Honoraria; LS has received speaker fees from AbbVie, Amgen, Almirall, Celgene, Celltrion, Eli Lilly, Galderma, Janssen-Cilag, Leo, Novartis, Pfizer, MSD and UCB. Grants/research support; LS has received grants/research funding from Pfizer. P. Gorecki: Other; PG is an employee of Janssen-Cilag Ltd.

Background Minimally invasive vertical tooth extraction techniques have evolved in light of the limitations of conventional tooth extraction techniques and flap surgery in preserving the alveolar bone. The authors conducted a study to obtain data on the performance of a vertical extraction system. This included comparing the need for flap surgery using the vertical extraction system versus conventional tooth extraction techniques for the extraction of anterior teeth and premolars not suitable for forceps extraction. Methods The authors conducted a prospective observational clinical study of the vertical extraction system versus conventional tooth extraction techniques using an interrupted time series in line with the Idea, Development, Exploration, Assessment, Long-term Follow-up collaboration framework for surgical innovation. Results Overall, 276 of 323 teeth (85.4%) in 240 patients were successfully extracted using the vertical extraction system. Of the 47 failures in the vertical tooth extraction cohort, 18 required flap surgery, resulting in an overall incidence of flap surgery of 5.6% (95% confidence interval [CI], 3.2% to 8.7%). During the routine care period, of the 94 anterior teeth and premolars in 78 patients, 21 teeth could not be extracted using conventional techniques and required flap surgery, leading to an incidence of flap surgery of 22% (95% CI, 14% to 32%). Conclusions The results suggest that the vertical extraction system may be used with a high success rate for extraction of severely destroyed teeth, and its use may lead to a marked reduction in the need for flap surgery. Randomized clinical trials are needed to confirm the findings. Practical Implications The use of a vertical extraction system may lower the incidence of flap surgery.

Lasers/LEDs demonstrate therapeutic effects for a range of biomedical applications. However, a consensus on effective light irradiation parameters and efficient and reliable measurement techniques remain limited. The objective here is to develop, characterise and demonstrate the application of LED arrays in order to progress and improve the effectiveness and accuracy of in vitro photobiomodulation studies. 96-well plate format LED arrays (400-850 nm) were developed and characterised to accurately assess irradiance delivery to cell cultures. Human dental pulp cells (DPCs) were irradiated (3.5-142 mW/cm2 : 15-120 s) and the biological responses were assessed using MTT assays. Array calibration was confirmed using a range of optical and analytical techniques. Multivariate analysis of variance revealed biological responses were dependent on wavelength, exposure time and the post-exposure assay time (P < 0.05). Increased MTT asbsorbance was measured 24 h post-irradiation for 30 s exposures of 3.5 mW/cm2 at 470, 527, 631, 655, 680, 777, 798 and 826 nm with distinct peaks at 631 nm and 798 nm (P < 0.05). Similar wavelengths were also effective at higher irradiances (48-142 mW/cm2 ). LED arrays and high throughput assays provide a robust and reliable platform to rapidly identify irradiation parameters which is both time- and cost-effective. These arrrays are applicable in photobiomodulation, photodynamic therapy and other photobiomedical research.

Summary Background & aims Surgical trauma leads to an inflammatory response that causes surgical morbidity. Reduced antioxidant micronutrient (AM) a levels and/or excessive levels of Reactive Oxygen Species (ROS) b have previously been linked to delayed wound healing and presence of chronic wounds. We aimed to evaluate the effect of pre-operative supplementation with encapsulated fruit and vegetable juice powder concentrate (JuicePlus+ ® ) on postoperative morbidity and Quality of Life (QoL) c . Methods We conducted a randomised, double-blind, placebo-controlled two-arm parallel clinical trial evaluating postoperative morbidity following lower third molar surgery. Patients aged between 18 and 65 years were randomised to take verum or placebo for 10 weeks prior to surgery and during the first postoperative week. The primary endpoint was the between-group difference in QoL over the first postoperative week, with secondary endpoints being related to other measures of postoperative morbidity (pain and trismus). Results One-hundred and eighty-three out of 238 randomised patients received surgery (Intention-To-Treat population). Postoperative QoL tended to be higher in the active compared to the placebo group. Furthermore, reduction in mouth opening 2 days after surgery was 3.1 mm smaller (95% CI 0.1, 6.1), the mean pain score over the postoperative week was 8.5 mm lower (95% CI 1.8, 15.2) and patients were less likely to experience moderate to severe pain on postoperative day 2 (RR 0.58, 95% CI 0.35, 0.95), comparing verum to placebo groups. Conclusion Pre-operative supplementation with a fruit and vegetable supplement rich in AM may improve postoperative QoL and reduce surgical morbidity and post-operative complications after surgery. Trial registration ClinicalTrials.gov Identifier: NCT01145820 ; Registered June 16, 2010.

Diclofenac sodium is a widely used nonsteroidal anti-inflammatory drug (NSAID) for relief of inflammatory pain. A recent formulation combines this drug with hydroxypropyl-β-cyclodextrin (HPβCD) to improve its solubility and to enable subcutaneous administration. Previous studies confirmed the efficacy of this combination. This study's aim was to evaluate the efficacy, safety, and local tolerability of diclofenac HPβCD administered as a local submucosal injection prior to lower third molar surgery. We conducted a prospective, randomized, double-blind, placebo-controlled, parallel-group phase II single-center study. Seventy-five patients requiring mandibular third molar surgery were randomized into 1 of 5 groups: 5 mg/1 mL diclofenac HPβCD, 12.5 mg/1 mL diclofenac HPβCD, 25 mg/1 mL diclofenac HPβCD, 50 mg/1 mL diclofenac HPβCD, or 1 mL placebo. The respective study drug was injected into the mucosal tissue surrounding the surgical site prior to surgery following achievement of local anesthesia. The primary outcome measure was the area under the curve (AUC) of cumulative pain scores from end of surgery to 6 h postsurgery. This demonstrated a global treatment effect between the active groups and placebo, hence confirming the study drug's efficacy ( P = 0.0126). Secondary outcome measures included the time until onset of pain and the time until patients required rescue medication, both showing statistical significance of the study drug compared to placebo ( P < 0.0161 and P < 0.0001, respectively). The time until rescue medication ranged between 7.8 h (for 25 mg/1 mL diclofenac HPβCD) and 16 h (for 50 mg/1 mL diclofenac HPβCD). Interestingly, the 5-mg/1-mL solution appeared superior to the 12.5-mg/1-mL and 25-mg/1-mL solutions (time until rescue medication = 12.44 h). A total of 14% of patients experienced minor adverse drug reactions (ADRs), of which 2 cases demonstrated flap necrosis. These resolved without further intervention. The study results overall indicate efficacy, safety, and relative tolerability of diclofenac HPβCD used locally as a submucosal injection prior to third molar surgery (ClinicalTrials.gov NCT01706588).

Even though increasing knowledge is emerging about synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome its pathogenesis remains enigmatic. Women are preferentially affected by SAPHO syndrome. Here we present the case of a 39-year-old woman suffering from this syndrome whose bone involvement was first interpreted as diffuse sclerosing osteomyelitis of the mandible. As treatment with clindamycin did not improve the symptoms, the decision was made to administer bisphosphonates intravenously. This treatment led to a rapid improvement in symptoms, which could be explained by the apparent tendency of bisphosphonates to exert a positive effect on the jaw. With this case report we attempt to offer an explanation for the influence of this group of medications on patients suffering from SAPHO syndrome with mandibular involvement.

The present study evaluated the relevance of EGFR overexpression in prediction of malignant transformation of oral leukoplakia (OLP). The retrospective study comprised paraffin-embedded tissue samples of OLP that transformed into oral squamous cell carcinoma (OSCC) (n=53) and tissue samples of OLP that did not transform into OSCC (n=45) during a follow-up period of 5 years. EGFR overexpression was assessed immunohistochemically. A significantly different expression rate of EGFR was determined between transformed and non-transformed OLP (p=0.017). A statistically significant increase of EGFR expression for low dysplasia lesions in group I compared to group II was proven (D0, p=0.013; D1, p=0.049). By calculation of ROC curve and determination of highest Youden index the optimal threshold value [cut-off point (COP) = 44.96] for distinguishing the transformed from non-transformed lesions was estimated (critical expression rate of EGFR). Using the determined COP the correlation between high-risk lesions and the detection of increased expression rates were significant (p=0.001). In the future, the assessment of EGFR overexpression in OLP may allow identifying OLP lesions with an increased risk of malignant transformation that may have been regarded harmless when only the grade of dysplasia had been taken into account.

Low level laser/light therapy (LLLT) or photobiomodulation is a biophysical approach that can be used to reduce pain, inflammation and modulate tissue healing and repair. However, its application has yet to be fully realized for dental disease treatment. The aim of this study was to assess the modulation of dental pulp cell (DPC) responses using two LLLT lasers with wavelengths of 660nm and 810nm. Human DPCs were isolated and cultured in phenol-red-free α- MEM/10%-FCS at 37°C in 5% CO 2 . Central wells of transparent-based black walled 96-microplates were seeded with DPCs (passages 2-4; 150μL; 25,000 cell/ml). At 24h post-seeding, cultures were irradiated using a Thor Photomedicine LLLT device (THOR Photomedicine, UK) at 660nm (3, 6 or 13s to give 2, 5 and 10J/cm 2 ) or 810nm (for 1, 2 or 5s to deliver 5, 10 and 20J/cm 2 ). Metabolic activity was assessed via a modified MTT assay 24h post-irradiation. Statistical differences were identified using analysis of variance and post-hoc Tukey tests (P=0.05) and compared with nonirradiated controls. Significantly higher MTT activity was obtained for both lasers (P 2 ). The MTT response significantly decreased (P 0.05). Consequently, enhanced irradiation parameters was apparent for both lasers. These parameters should be further optimised to identify the most effective for therapeutic application.

Scleroderma is an uncommon connective-tissue disease, its key feature being excessive collagen deposition resulting in fibrosis of the skin and internal organs. There are different types that can vary in severity from localized scleroderma to systemic sclerosis. Various clinical and radiographic findings can be attributed to the disease, which arise owing to the progressive nature of microvascular changes and collagen deposition. These include limited mouth opening, xerostomia, periodontal disease and cardiac and pulmonary disease. Whilst bone resorption has been reported, as far as we are aware, the literature has not described a case with failure of bony suture closure. Hence, we would like to describe what is probably a unique case of a patient with a 5-year history of systemic sclerosis, who was referred for management of increased mobility of her upper central incisors. Radiographic imaging (conventional and three-dimensional) confirmed increased bone resorption, partly owing to periodontal disease, but also owing to an open premaxillary suture. Similarly, other craniofacial sutures were diagnosed as being open, and, to our knowledge, this represents a yet undescribed finding in a patient suffering from scleroderma.

The study aimed at checking if MAGE-A expression in oral leukoplakia (OLP) lesions is related to malignant transformation. The 48 samples of OLP that transformed to oral squamous cell carcinoma (OSCC) (group 1) and 50 samples of OLP that did not transform to OSCC (group 2) were included in the study. The expression of MAGE-A was restricted to group 1. The correlation between malignant transformation and MAGE-A occurrence in OLP was statistically significant (p < .0001). Detection of MAGE-A may allow identifying OLP with a high risk of malignant transformation giving a view to a new approach to prevention of oral cancer.