Symptom-based stratification of patients with primary Sjögren's syndrome: multi-dimensional characterisation of international observational cohorts and reanalyses of randomised clinical trials

Background Heterogeneity is a major obstacle to developing effective treatments for patients with primary Sjögren's syndrome. We aimed to develop a robust method for stratification, exploiting heterogeneity in patient-reported symptoms, and to relate these differences to pathobiology and therapeutic response. Methods We did hierarchical cluster analysis using five common symptoms associated with primary Sjögren's syndrome (pain, fatigue, dryness, anxiety, and depression), followed by multinomial logistic regression to identify subgroups in the UK Primary Sjögren's Syndrome Registry (UKPSSR). We assessed clinical and biological differences between these subgroups, including transcriptional differences in peripheral blood. Patients from two independent validation cohorts in Norway and France were used to confirm patient stratification. Data from two phase 3 clinical trials were similarly stratified to assess the differences between subgroups in treatment response to hydroxychloroquine and rituximab. Findings In the UKPSSR cohort (n=608), we identified four subgroups: Low symptom burden (LSB), high symptom burden (HSB), dryness dominant with fatigue (DDF), and pain dominant with fatigue (PDF). Significant differences in peripheral blood lymphocyte counts, anti-SSA and anti-SSB antibody positivity, as well as serum IgG, κ-free light chain, β2-microglobulin, and CXCL13 concentrations were observed between these subgroups, along with differentially expressed transcriptomic modules in peripheral blood. Similar findings were observed in the independent validation cohorts (n=396). Reanalysis of trial data stratifying patients into these subgroups suggested a treatment effect with hydroxychloroquine in the HSB subgroup and with rituximab in the DDF subgroup compared with placebo. Interpretation Stratification on the basis of patient-reported symptoms of patients with primary Sjögren's syndrome revealed distinct pathobiological endotypes with distinct responses to immunomodulatory treatments. Our data have important implications for clinical management, trial design, and therapeutic development. Similar stratification approaches might be useful for patients with other chronic immune-mediated diseases. Funding UK Medical Research Council, British Sjogren's Syndrome Association, French Ministry of Health, Arthritis Research UK, Foundation for Research in Rheumatology

Arthroscopic Anatomic Glenoid Reconstruction in Lateral Decubitus Position Using Allograft With Nonrigid Fixation

Recurrent shoulder instability is highly associated with glenoid bone loss. Traditionally, bony procedures to address this bone loss have described nonanatomic, coracoid transfer procedures. More recently, anatomic glenoid reconstruction procedures have been described. These were first described as open procedures, and subsequently there have been several arthroscopic procedures described. We provide a description of an arthroscopic anatomic glenoid reconstruction approach with allograft

Arthroscopic Anatomic Glenoid Reconstruction With Bankart Repair and Remplissage for Recurrent Anterior Shoulder Instability with Bipolar Bone Loss

After first-time dislocation, the recurrence of instability requires less force as the result of associated injury of soft-tissue and bony stabilizing structures. Bone loss of either/both the glenoid and humeral head increases the risk of redislocation even after initial isolated soft-tissue stabilization. Several arthroscopic procedures have been described to address each of these pathologies individually. When combined, they address all pathologies in a single surgery and restore stability, reducing the need for a secondary procedure. This Technical Note describes an all-arthroscopic anatomic glenoid reconstruction with Bankart repair plus remplissage

Posterior Arthroscopic Anatomic Glenoid Reconstruction

Posterior bone loss following posterior instability of the shoulder can lead to poor patient outcomes and increased likelihood of subsequent dislocations. Unlike in cases of anterior instability, the critical amount of bone loss that warrants surgical intervention in posterior instability has not been established. Posterior instability and bone loss are commonly seen in traumatic settings where cumulative dislocations occur. Similar to surgical treatment of anterior instability, both arthroscopic and open procedures have been used, with the former gaining momentum as the preferred method. To address resultant bone loss, surgeons can use a variety of grafting techniques and sources for augmentation of the posterior glenoid deficit. Here we describe an adaptation of the arthroscopic anatomic glenoid reconstruction for posterior instability with bone loss using a distal tibia allograft. This arthroscopic technique allows for excellent surgical visualization, graft delivery, and anatomic reconstruction of the articular surface of the glenoid

Revision of Failed Arthroscopic Anatomic Glenoid Reconstruction Fixed With Suture Button to Arthroscopic Anatomic Glenoid Reconstruction Fixed With Screw Fixation

Arthroscopic anatomic glenoid reconstruction (AAGR) is an evolving technique for addressing recurrent anterior glenohumeral instability. Despite advances from the original surgical technique, the use of button fixation has raised considerable concerns because of higher rates of clinical failure, necessitating revision procedures. This article describes revision of AAGR using screw fixation after failed primary AAGR with button fixation. We outline a stepwise approach to guide the decision-making process and identify perioperative technical challenges in revising a previously reconstructed glenoid