University Hospitals Birmingham NHS Foundation Trust

Accurate registration of multi-stained whole-slide images (WSIs) enables the integration of complementary morphological and molecular information, improving both clinical diagnostic and prognostic analysis. It also enables efficient transfer of annotations between consecutive or re-stained slides, significantly reducing annotation time and cost, as well as three-dimensional tissue reconstruction. Despite its importance, WSI registration remains challenging due to variations in slide preparation across stains and complex tissue deformations. Existing methods are often tailored to specific staining modalities and fail to generalize across diverse settings, highlighting the need for a robust and generalizable cell-level multi-stain registration method. In this work, we introduce CORE, a novel coarse-to-fine framework for accurate cell-centric registration across six multimodal WSI datasets, encompassing 30 distinct staining types, including Hematoxylin & Eosin (H&E), periodic acid–Schiff (PAS), multiplex immunohistochemistry (mIHC), multiplex immunofluorescence (mIF) and Cyclic immunofluorescence (Cyc-IF). CORE first performs coarse global registration by extracting tissue masks through prompt-based segmentation to remove artifacts and non-tissue regions, followed by rigid alignment using tissue morphology and a pre-trained feature extractor. The resulting alignment is refined using a shape-aware point-set registration model applied to automatically detected nuclei centroids, enabling fine-grained rigid alignment. Finally, Coherent Point Drift (CPD) is used to estimate a non-linear displacement field for non-rigid cellular alignment. Using nuclei correspondences throughout the pipeline, CORE achieves accurate and robust cell-level alignment across modalities.Experimental results show that CORE consistently outperforms state-of-the-art methods in accuracy, robustness, and generalization across both bright-field and immunofluorescence WSIs.

The 16th Acromegaly Consensus Conference in September 2024 updated recommendations on diagnosis and treatment of acromegaly comorbidities. Since the 2020 acromegaly comorbidity management guideline was published, new evidence has emerged on novel and known comorbidities and new treatment approaches. Forty-three experts in the management of acromegaly reviewed the current literature and assessed changes in clinical practice standards and management. Current outcome goals were considered and updated, with a focus on the impact of current and emerging treatments of these comorbidities. Participants assessed factors that determine pharmacological choices, as well as use of specific agents in the management of the most relevant acromegaly comorbidities. We present consensus recommendations highlighting optimization of evidence-based acromegaly comorbidities management.

Osteoporosis, a condition marked by increased fracture risk, remains under-diagnosed and under-treated worldwide, resulting in a substantial "treatment gap"-the difference between those eligible for osteoporosis treatment and those who actually receive it. While the concept of closing the treatment gap is commendable, and has galvanized clinical and policy efforts, this position statement argues that the prevailing narrative is in danger of becoming disease-focused and parentalistic, neglecting person-centered care. An international consensus group, including public contributors with lived experience were convened to define and characterize the "osteoporosis care gap" as a broader framework, encompassing deficits not only in pharmacological treatment but also in diagnosis, assessment, and multi-disciplinary management. The care gap is thus defined as "the discrepancy between the care provided to those at risk of osteoporotic fractures and best practice, person-centered care." Multi-level determinants of the care gap are identified including: societal-low public awareness underpinned by unhelpful stereotypes, and prevalent health inequalities; health policy-insufficient prioritization, diagnostic confusion, and lack of incentivization; healthcare service-fragmented care pathways with unclear roles and poor communication, inadequate follow-up, and insufficient support for shared decision making; and individual-unmet needs for care which is person-centered, participatory, understandable, equitable, holistic and multidisciplinary, and respects autonomy. The statement calls for a person-centered, equitable, and multidisciplinary approach to osteoporosis care, integrating the perspectives and needs of patients, families, and caregiver. Actions needed at societal and policy level are described, including increasing public awareness, increasing health policy prioritization, with clear professional leadership. The components of osteoporosis care are described in terms of case finding, assessment, treatment, and review. Addressing this, care gap requires coordinated efforts from policymakers, healthcare services, and professionals, with a renewed focus on equity and patient values and preferences.

BACKGROUND AND OBJECTIVES:The genetic basis of multiple sclerosis (MS) susceptibility has been studied extensively in European (EUR) ancestry populations. The aim of our study was to determine the genetic architecture of MS susceptibility in people of South Asian (SAS) and African (AFR) genetic ancestral backgrounds. METHODS:We recruited and genotyped a cohort of ancestrally diverse people with MS (pwMS) from across the United Kingdom. Cases were combined with controls from the UK Biobank (UKB). After genetic ancestry inference, we performed within-ancestry case-control genetic association studies of MS susceptibility, exploring single nucleotide variants and imputed classical human leukocyte antigen alleles. RESULTS:We analyzed genetic data from 676 pwMS from our cohort (median age = 45.7 years, 71.7% female genetic sex), 2,426 pwMS from the UKB (median age = 55.0 years, 72.3% female), and 27,640 UKB controls (median age = 54.0 years, 52.5% female). Genetic variants within the Major Histocompatibility Complex were associated with MS susceptibility across all ancestries (SAS: lead SNP chr6:32635095:G:C, odds ratio [OR] = 1.7, p = 4.2 × 10-8, nearest gene HLA-DQA1; AFR: lead SNP chr6:32593550:T:C, OR = 1.7, p = 1.2 × 10-5, nearest gene HLA-DRB1). EUR ancestry susceptibility alleles were over-represented in cases from both ancestries, with the degree of concordance stronger for the SAS (ρ = 0.46, p = 8.3 × 10-9) than the AFR (ρ = 0.35, Spearman p = 2.5 × 10-5) ancestry cohort. EUR-derived genetic risk scores performed better than chance but less well than in EUR ancestry cohorts, explaining 3.9% (SAS, p = 1.0 × 10-4) and 1.9% (AFR, p = 2.0 × 10-4) of the liability to MS, contrasting with 9.6% (empirical p = 1.0 × 10-4) in the EUR cohort. Several classical human leukocyte antigen (HLA) alleles associated with MS in EUR ancestry populations show similar effects in SAS and AFR ancestry cohorts, including HLA-DRB1*15:01; however, the population-level risk explained by this allele is lower in SAS (8.8%) and AFR (2.9%) cohorts than in EUR cohorts due to allele frequency. We found some evidence for a protective role for the SAS-enriched HLA-A*33:03 allele in the SAS cohort, which has not been previously described. DISCUSSION:The genetic architecture of MS susceptibility shows strong concordance across ancestral groups suggesting shared disease mechanisms. Larger studies in diverse populations are likely to enhance our understanding of how genetic variation contributes to MS susceptibility in people of all ancestral backgrounds.

Aims:In the Scaphoid Waist Internal Fixation for Fractures Trial (SWIFFT), surgical fixation was compared with cast immobilization, with the primary endpoint being the outcomes at one year. The aim of the current study was to assess the radiological outcomes (union and the development of osteoarthritis (OA)) of the two forms of treatment at five years. Methods:Patients who remained in the trial at five years after randomization were invited to have plain radiographs and a CT scan of the injured wrist, and a posterior-anterior radiograph of the contralateral wrist. This imaging was reviewed by three observers independently for union of the fracture and the distribution and severity of OA. This analysis followed a pre-specified statistical analysis plan. The relationship between OA and the Patient-Rated Wrist Evaluation (PRWE) scores at five years was assessed. Results:Of the 439 patients who were randomized, 267 (60.8%) provided imaging at five years. Their characteristics were similar to those of the original cohort. A total of 182 patients (68.2%) (n = 92 fixation, n = 90 cast) had complete union and seven had a nonunion (2.6%; n = 3 fixation, n = 4 cast). Fractures with a minimum of 20% union at one year consolidated with the passage of time without intervention. Progression of OA in the joints around the scaphoid was seen in both groups from baseline to five years. By five years, 140 patients (52.4% of those with imaging at five years) had OA in at least one joint with similar prevalences in both groups. The prevalence of OA, the number of arthritic joints and the maximum severity of OA, was similar in the two groups. A total of 344 of the initial cohort of 439 patients (78.4%) provided a valid PRWE score at five years and the mean score was higher in those with more severe OA, indicating worse pain and function. Conclusion:Between one and five years after randomization, union consolidated in those with > 20% bridging without intervention. The proportion of patients with full, almost full, partial, slight, and nonunion for the two forms of treatment remained similar at five years. The prevalence and severity of OA increased during the five years but was similar in both groups.