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Abstract Background Guselkumab, a fully human monoclonal antibody targeting the interleukin (IL)-23p19 subunit, is approved to treat adults with active psoriatic arthritis (PsA). In the Phase 3 DISCOVER-2 trial of 739 bilogico-naïve patients with active PsA, guselkumab 100 mg resulted in less radiographic progression, assessed via change from baseline in PsA-modified van der Heijde-Sharp (vdH-S) score, compared with placebo at week (W) 24 when given at W0, W4, and then every 4 weeks (Q4W) or Q8W. The least squares mean differences from placebo were -0.66 for guselkumab Q4W (p=0.011) and -0.43 for guselkumab Q8W (p=0.072). Reports suggest baseline C-reactive protein (CRP) and joint erosions are strongly prognostic of poor outcomes, especially radiographic progression, in PsA patients. We designed a trial (APEX) to further assess the effect of guselkumab on radiographic progression in patients with active PsA and risk factors for radiographic progression. Methods Patients are eligible for APEX if they have had PsA for ≥6 months and active disease (≥3 swollen and ≥3 tender joints, CRP ≥0.3 mg/dL) despite prior therapy with conventional synthetic disease-modifying antirheumatic drugs, apremilast, and/or nonsteroidal anti-inflammatory drugs, with ≥2 joints with erosions on baseline radiographs (hands and feet). The primary and major secondary endpoints are the proportion of patients achieving ≥20% improvement in American College of Rheumatology response criteria (ACR20) response at W24 and change from baseline at W24 in PsA-modified vdH-S score, respectively. Sample sizes of 350/250/350 for guselkumab Q8W/guselkumab Q4W/placebo are expected to provide >99% power to detect significant differences in W24 ACR20 response rates for each guselkumab group vs placebo, as well as ≥90% (Q4W vs placebo) and ≥80% (Q8W vs placebo) power to detect a significant difference in PsA-modified vdH-S score change at W24. A Cochran-Mantel-Haenszel test and analysis of covariance will compare treatment efficacy for the primary and major secondary endpoints, respectively. Discussion DISCOVER-2 findings informed the design of APEX, a Phase 3b study intended to further evaluate the impact of guselkumab in patients with active PsA and known risk factors for radiographic progression. Trial registration This trial was registered at ClinicalTrials.gov, NCT04882098 . Registered on 11 May 2021.

Background: Guselkumab, a fully human monoclonal antibody targeting the interleukin (IL)-23p19 subunit, is approved to treat adults with active psoriatic arthritis (PsA). In the Phase 3 DISCOVER-2 trial of 739 bilogico-naïve patients with active PsA, guselkumab 100 mg resulted in less radiographic progression, assessed via change from baseline in PsA-modified van der Heijde-Sharp (vdH-S) score, compared with placebo at week (W) 24 when given at W0, W4, and then every 4 weeks (Q4W) or Q8W. The least squares mean differences from placebo were -0.66 for guselkumab Q4W (p=0.011) and -0.43 for guselkumab Q8W (p=0.072). Reports suggest baseline C-reactive protein (CRP) and joint erosions are strongly prognostic of poor outcomes, especially radiographic progression, in PsA patients. We designed a trial (APEX) to further assess the effect of guselkumab on radiographic progression in patients with active PsA and risk factors for radiographic progression. Methods: Patients are eligible for APEX if they have had PsA for ≥6 months and active disease (≥3 swollen and ≥3 tender joints, CRP ≥0.3 mg/dL) despite prior therapy with conventional synthetic disease-modifying antirheumatic drugs, apremilast, and/or nonsteroidal anti-inflammatory drugs, with ≥2 joints with erosions on baseline radiographs (hands and feet). The primary and major secondary endpoints are the proportion of patients achieving ≥20% improvement in American College of Rheumatology response criteria (ACR20) response at W24 and change from baseline at W24 in PsA-modified vdH-S score, respectively. Sample sizes of 350/250/350 for guselkumab Q8W/guselkumab Q4W/placebo are expected to provide >99% power to detect significant differences in W24 ACR20 response rates for each guselkumab group vs placebo, as well as ≥90% (Q4W vs placebo) and ≥80% (Q8W vs placebo) power to detect a significant difference in PsA-modified vdH-S score change at W24. A Cochran-Mantel-Haenszel test and analysis of covariance will compare treatment efficacy for the primary and major secondary endpoints, respectively. Discussion: DISCOVER-2 findings informed the design of APEX, a Phase 3b study intended to further evaluate the impact of guselkumab in patients with active PsA and known risk factors for radiographic progression. Trial registration: This trial was registered at ClinicalTrials.gov, NCT04882098. Registered on 11 May 2021. [ABSTRACT FROM AUTHOR]

Aim To identify phenotypes of periodontitis patients by the use of an unsupervised modelling technique (clustering), based on pre-treatment radiographic and microbiological characteristics. Materials and methods This retrospective study included data from 392 untreated periodontitis patients. Co-regularized spectral clustering algorithm was used to cluster the patients. The resulting clusters were subsequently characterized based on their demographics, radiographic bone loss patterns and microbial data. Results The vast majority of patients fitted into one of the three main clusters (accuracy 90%). Cluster A ( n = 18) was characterized by high prevalence and high proportions of Aggregatibacter actinomycetemcomitans, a trend for a more localized pattern of alveolar bone loss and young individuals. Clusters B ( n = 200) and C ( n = 135) differed clearly in disease severity patterns and smoking habits, but not in microbiological characteristics. Conclusion On the basis of alveolar bone loss patterns and microbiological data, untreated periodontitis patients can be clustered into at least three phenotypes. These results should be validated in other cohorts, and the clinical utility needs to be explored on the basis of periodontal treatment outcomes and/or disease progression. [ABSTRACT FROM AUTHOR]

Background To validate the concept of immediate implant placement and nonfunctional loading for use in the esthetically sensitive anterior maxilla, clinical trials should ideally include objective esthetic criteria. Purpose This study analyzed procedural results as graded by the pink esthetic score and white esthetic score (PES/WES). Methods Thirty-nine suitable patients (mean follow-up 44.82 ± 28 months) were evaluated. Results Thirty-eight implants fulfilled stringent criteria for successful osseointegration: absence of peri-implant radiolucency, implant mobility, suppuration, and pain. The mean total PES/WES was 15.50 ± 2.67 (range: 10-20). The mean total PES of 7.92 ± 1.60 (range: 5-10) indicated favorable overall peri-implant soft-tissue conditions. Root convexity and texture (1.63 ± 0.54) and curvature of the facial mucosa (1.68 ± 0.47) and distal papilla (1.66 ± 0.48) had the highest mean values, whereas acceptable levels of facial tissue (1.53 ± 0.73) and mesial papilla (1.42 ± 0.64) were the most difficult to fully achieve. The mean mesial and distal bone loss at data collection was, was 1.19 ± 0.54 and 1.15 ± 0.51, respectively. Periodontal disease severity (advanced chronic and aggressive periodontitis) was significantly associated with a low total PES ( p = .048). Conclusions Objective PES/WES assessment validated immediate anterior maxillary single-tooth replacement and restoration as being a successful and esthetically predictable treatment modality in sites where the buccal bone had been preserved during the extraction at 1 year of follow-up. [ABSTRACT FROM AUTHOR]

Objectives Radiologic and biologic assessment of immediately restored Implants combined with guided bone regeneration (GBR) and free connective tissue graft. Methods 1-4 year retrospective study involving 34 patients treated with maxillary immediately restored anterior single-implants. Soft tissue dimensions, radiographic bone loss, and biological and prosthetic complications were assessed. Results During the mean follow up period of 29 months the study group presented a mean mesial bone loss of 1.10 ± 0.39 mm (range: 0.5-2.4 mm), and mean distal bone loss of 1.19 ± 0.41 mm (range: 0.4-2.1 mm). Mean periimplant probing depth of 3.49 mm (SD ± 1.06) and 2.35 (SD ± 0.52) for the contralateral tooth (highly significant p < 0.001). Bleeding on probing was present in 29.4% of the examined implant supported crown sites and 10.4% of the contralateral teeth ( p < 0.001). Conclusions Anterior maxillary single-tooth replacement, using GBR and connective tissue graft according to the concept of immediate implant placement, and non-functional restoration is an accepted treatment modality achieving favorable peri-implant soft tissue condition. [ABSTRACT FROM AUTHOR]

Study Design: A prospective comparative study. Objective: This study aimed to establish cervical spine morphometry, alignment, and range of motion (ROM) and to clarify the impact of these age-related and degenerative changes. Summary Of Background Data: There are no studies that have evaluated differences in the results of cervical spine radiographs between a large series of cervical spondylotic myelopathy (CSM) patients and healthy subjects. Methods: We enrolled 1016 consecutive CSM patients who underwent laminoplasty. CSM patients were also divided based on each decade of life between the fourth and ninth decades. We also enrolled a total of 1230 healthy volunteers as asymptomatic subjects in this study. There were at least 100 men and 100 women in each decade of life between the third and eighth decades. Cervical sagittal alignment on neutral and flexion-extension views was measured by the Cobb method at C2-7. ROM was assessed by measuring the difference in alignment between flexion and extension. Results: Cervical lordosis in the neutral position increased gradually with age in both groups. CSM patients showed significantly smaller lordotic angles compared with those shown by asymptomatic subjects within each decade. The total ROM decreased with increasing age in both groups. The total ROM of females was larger than males. The ROM of CSM patients was significantly smaller than asymptomatic subjects. The flexion ROM did not change with aging in either group. There was no significant difference in the flexion ROM between males and females in the two groups. However, the extension ROM decreased gradually in both groups. The extension ROM of CSM patients was significantly smaller than asymptomatic subjects. Conclusion: Age-related and degenerative changes in the cervical spine, alignment, and ROM in each decade of life were established between CSM patients and asymptomatic subjects. [ABSTRACT FROM AUTHOR]