Development of international consensus on a standardised image acquisition protocol for diagnostic evaluation of the sacroiliac joints by MRI: an ASAS-SPARTAN collaboration.

BACKGROUND: A range of sacroiliac joint (SIJ) MRI protocols are used in clinical practice but not all were specifically designed for diagnostic ascertainment. This can be confusing and no standard diagnostic SIJ MRI protocol is currently accepted worldwide. OBJECTIVE: To develop a standardised MRI image acquisition protocol (IAP) for diagnostic ascertainment of sacroiliitis. METHODS: 13 radiologist members of Assessment of SpondyloArthritis International Society (ASAS) and the SpondyloArthritis Research and Treatment Network (SPARTAN) plus two rheumatologists participated in a consensus exercise. A draft IAP was circulated with background information and online examples. Feedback on all issues was tabulated and recirculated. The remaining points of contention were resolved and the revised IAP was presented to the entire ASAS membership. RESULTS: A minimum four-sequence IAP is recommended for diagnostic ascertainment of sacroiliitis and its differential diagnoses meeting the following requirements. Three semicoronal sequences, parallel to the dorsal cortex of the S2 vertebral body, should include sequences sensitive for detection of (1) changes in fat signal and structural damage with T1-weighting; (2) active inflammation, being T2-weighted with fat suppression; (3) bone erosion optimally depicting the bone-cartilage interface of the articular surface and (4) a semiaxial sequence sensitive for detection of inflammation. The IAP was approved at the 2022 ASAS annual meeting with 91% of the membership in favour. CONCLUSION: A standardised IAP for SIJ MRI for diagnostic ascertainment of sacroiliitis is recommended and should be composed of at least four sequences that include imaging in two planes and optimally visualise inflammation, structural damage and the bone-cartilage interface.

Features of Axial Spondyloarthritis in Two Multicenter Cohorts of Patients with Psoriasis, Uveitis, and Colitis Presenting with Undiagnosed Back Pain.

OBJECTIVE: We aimed to assess: 1. The frequency of axial spondyloarthritis (axSpA) according to extra-articular presentation and HLA-B27 status; 2. Clinical and imaging features that distinguish axSpA from non-axSpA; 3. The impact of MRI on diagnosis and classification of axSpA. METHODS: The Screening in Axial Spondyloarthritis in Psoriasis, Iritis, Colitis, (SASPIC) study enrolled patients in two multicenter cohorts. Consecutive patients with undiagnosed chronic back pain attending dermatology, ophthalmology, and gastroenterology clinics with PsO, AAU, or IBD, were referred to a local rheumatologist with special expertise in axSpA for a structured diagnostic evaluation. The primary outcome was proportion of patients diagnosed with axSpA by final global evaluation. RESULTS: Frequency of axSpA was 46.7%, 61.6%, and 46.8% in SASPIC-1 cases (n=212) and 23.5%, 57.9%, and 23.3% in SASPIC-2 cases (n=151) with PsO, AAU, or IBD, respectively. Among B27 positives, axSpA was diagnosed in 70%, 74.5%, and 66.7% in SASPIC-1, and in 71.4%, 87.8%, and 55.6% in SASPIC-2 in patients with PsO, AAU, or IBD, respectively. All musculoskeletal clinical features were non-discriminatory. MRI was indicative of axSpA in 60-80% of patients and MRI in all patients (SASPIC-2) versus on-demand (SASPIC-1) led to 25% fewer diagnoses of axSpA in HLA B27 negatives with PsO or IBD. Performance of the ASAS classification criteria was greater with routine MRI (SASPIC-2) though sensitivity was lower than previously reported. CONCLUSIONS: Optimal management of patients presenting with PsO, AAU, IBD, and undiagnosed chronic back pain should include referral to a rheumatologist. Conducting MRI in all patients enhances diagnostic accuracy.

Identifying and prioritizing recommendations to optimize transitions across the care journey for hip fractures: Results from a mixed-methods concept mapping study.

BACKGROUND: Individuals who experience a hip fracture have numerous care transitions. Improving the transition process is important for ensuring quality care; however, little is known about the priorities of different key interest groups. Our aim was to gather recommendations from these groups regarding care transitions for hip fracture. METHODS: We conducted a concept mapping study, inviting persons with lived experience (PWLE) who had a hip fracture, care partners, healthcare providers, and decision-makers to share their thoughts about 'what is needed to improve care transitions for hip fracture'. Individuals were subsequently asked to sort the generated statements into conceptual piles, and then rate by importance and priority using a five-point scale. Participants decided on the final map, rearranged statements, and assigned a name to each conceptual cluster. RESULTS: A total of 35 participants took part in this concept mapping study, with some individuals participating in multiple steps. Participants included 22 healthcare providers, 7 care partners, 4 decision-makers, and 2 PWLE. The final map selected by participants was an 8-cluster map, with the following cluster labels: (1) access to inpatient services and supports across the care continuum (13 statements); (2) informed and collaborative discharge planning (13 statements); (3) access to transitional and outpatient services (3 statements); (4) communication, education and knowledge acquisition (9 statements); (5) support for care partners (2 statements); (6) person-centred care (13 statements); (7) physical, social, and cognitive activities and supports (13 statements); and (8) provider knowledge, skills, roles and behaviours (8 statements). CONCLUSIONS: Our study findings highlight the importance of person-centred care, with active involvement of PWLE and their care partners throughout the care journey. Many participant statements included specific ideas related to continuity of care, and clinical knowledge and skills. This study provides insights for future interventions and quality improvement initiatives for enhancing transitions in care among hip fracture populations.

Timing of follow-up visits after hospital discharge for COPD: Application of a new method.

RATIONALE: A common strategy to reduce COPD readmissions is to encourage patient follow-up with a physician within 1 to 2 weeks of discharge, yet evidence confirming its benefit is lacking. We used a new study design called target randomized trial emulation to determine the impact of follow-up visit timing on patient outcomes. METHODS: All Ontario residents aged 35 or older discharged from a COPD hospitalization were identified using health administrative data and randomly assigned to those who received and did not receive physician visit follow-up by within seven days. They were followed to all-cause emergency department visits, readmissions or death. Targeted randomized trial emulation was used to adjust for differences between the groups. COPD emergency department visits, readmissions or death was also considered. RESULTS: There were 94,034 patients hospitalized with COPD, of whom 73.5% had a physician visit within 30 days of discharge. Adjusted hazard ratio for all-cause readmission, emergency department visits or death for people with a visit within seven days post discharge was 1.03 (95% Confidence Interval [CI]: 1.01-1.05) and remained around 1 for subsequent days; adjusted hazard ratio for the composite COPD events was 0.97 (95% CI 0.95-1.00) and remained significantly lower than 1 for subsequent days. CONCLUSION: While a physician visit after discharge was found to reduce COPD events, a specific time period when a physician visit was most beneficial was not found. This suggests that follow-up visits should not occur at a predetermined time but be based on factors such as anticipated medical need.

Spinal Lesions in Axial Psoriatic Disease: How Should They Be Identified and Quantified by Magnetic Resonance Imaging?

Proper assessment of patients with psoriatic arthritis (PsA) requires assessment of all disease domains, including axial disease. Magnetic resonance imaging (MRI) is the method of choice for evaluating axial involvement in PsA. When assessing patients with PsA for spinal involvement, it is important to assess both vertebral body lesions and posterolateral lesions, such as inflammation in facet joints and costovertebral joints, and enthesitis at spinous and transverse processes. The Canada-Denmark (CanDen) assessment system for spine MRIs is the preferred method for detailed evaluation of inflammation and structural damage at various anatomical locations in the spine, and it is reproducible and sensitive to change. The Assessment of Spondyloarthritis international Society (ASAS) has recently published MRI definitions of inflammatory and structural lesions in the spine, incorporating the CanDen definitions of spinal lesions on MRI. Applying the ASAS definitions and the CanDen assessment system in clinical practice and trials is recommended. Ongoing research/studies, not least the Axial Involvement in Psoriatic Arthritis (AXIS) study, may provide a data-driven definition of axial involvement in PsA. Ongoing research is expected to further improve and validate assessment tools for axial PsA and to provide a much-needed data-driven consensus-based definition of axial involvement in PsA.

Chiral multiferroicity in two-dimensional hybrid organic-inorganic perovskites.

Chiral multiferroics offer remarkable capabilities for controlling quantum devices at multiple levels. However, these materials are rare due to the competing requirements of long-range orders and strict symmetry constraints. In this study, we present experimental evidence that the coexistence of ferroelectric, magnetic orders, and crystallographic chirality is achievable in hybrid organic-inorganic perovskites [(R/S)-ß-methylphenethylamine]2CuCl4. By employing Landau symmetry mode analysis, we investigate the interplay between chirality and ferroic orders and propose a novel mechanism for chirality transfer in hybrid systems. This mechanism involves the coupling of non-chiral distortions, characterized by defining a pseudo-scalar quantity, ξ = p ⋅ r ( p represents the ferroelectric displacement vector and r denotes the ferro-rotational vector), which distinguishes between (R)- and (S)-chirality based on its sign. Moreover, the reversal of this descriptor's sign can be associated with coordinated transitions in ferroelectric distortions, Jahn-Teller antiferro-distortions, and Dzyaloshinskii-Moriya vectors, indicating the mediating role of crystallographic chirality in magnetoelectric correlations.

Classification Criteria for Axial Disease in Youth with Juvenile Spondyloarthritis.

OBJECTIVES: To develop and validate classification criteria for axial disease in youth with juvenile spondyloarthritis (SpA; AxJSpA). METHODS: This international initiative consisted of four phases: 1) Item generation; 2) Item reduction; 3) Criteria development; and 4) Validation of the AxJSpA criteria by an independent team of experts in an internationally representative Validation cohort. RESULTS: These criteria are intended to be used on youth with a physician diagnosis of juvenile SpA and for whom axial disease is suspected. Item generation consisted of a systematic literature review and a free-listing exercise using input from international physicians and collectively resulted in 108 items. After the item reduction exercise and expert panel input, 37 items remained for further consideration. The final AxJSpA criteria domains included: imaging: active inflammation, imaging: structural lesions, pain chronicity, pain pattern, pain location, stiffness, and genetics. The most heavily weighted domains were active inflammation and structural lesions on imaging. Imaging typical of sacroiliitis was deemed necessary, but not sufficient, to classify a youth with AxJSpA. The threshold for classification of AxJSpA was a score of ≥55 (out of 100). When tested in the validation data set, the final criteria had a specificity of 97.5% (95% CI: 91.4-99.7), sensitivity of 64.3% (95% CI: 54.9-73.1) and Area Under the Receiver Operating Characteristic (AUROC) curve of 0.81 (95% CI: 0.76-0.86). CONCLUSIONS: The new AxJSpA classification criteria require an entry criterion, physician diagnosis of juvenile SpA, and include seven weighted domains. The AxJSpA classification criteria are validated and designed to identify participants for research studies.

Matching-Adjusted Indirect Comparison of the 52-Week Efficacy of Bimekizumab Versus Secukinumab and Ixekizumab for the Treatment of Radiographic Axial Spondyloarthritis.

INTRODUCTION: A previous network meta-analysis established 16-week relative efficacy with bimekizumab, an inhibitor of interleukin (IL)-17F in addition to IL-17A, versus other treatments for patients with radiographic axial spondyloarthritis (r-axSpA; i.e., ankylosing spondylitis), including the IL-17A inhibitors secukinumab and ixekizumab. This matching-adjusted indirect comparison (MAIC) assessed 52-week relative efficacy of bimekizumab versus secukinumab and ixekizumab. METHODS: Individual patient data from BE MOBILE 2 (bimekizumab 160 mg; N = 220) were matched to pooled summary data from MEASURE 1/2/3/4 (secukinumab 150 mg), MEASURE 3 (secukinumab 300 mg; escalated dose for inadequate responders), COAST-V (ixekizumab) and COAST-V/-W (ixekizumab). BE MOBILE 2 patients were reweighted using propensity score weights based on age, sex, ethnicity, tumor necrosis factor inhibitor (TNFi) exposure, weight, baseline ASDAS and BASFI (secukinumab) and baseline BASDAI (ixekizumab), and 52-week efficacy outcomes from the trial recalculated. Odds ratios (OR) or mean difference for unanchored comparisons are reported with 95% confidence intervals (CI). RESULTS: At week 52, MAIC demonstrated that patients may have higher likelihood of improvement in key efficacy outcomes with bimekizumab versus secukinumab 150 mg (e.g., ASAS40: [OR (95% CI): 1.48 (1.05, 2.10); p = 0.026]; effective sample size [ESS] = 177). Differences in 52-week efficacy outcomes between bimekizumab and secukinumab 300 mg dose escalation were non-significant (ESS = 120). Bimekizumab versus ixekizumab 80 mg comparisons (COAST-V only; ESS = 84) also suggested that differences were non-significant for most key efficacy outcomes. Other ixekizumab comparisons (COAST-V/-W; ESS = 45) suggested bimekizumab may have higher comparative efficacy for many of the same efficacy outcomes, however ixekizumab analyses were limited by poor population overlap, likely due to the greater proportion of patients with previous TNFi exposure. CONCLUSIONS: Patients treated with bimekizumab may have a higher likelihood of achieving improved longer-term efficacy versus secukinumab 150 mg, suggesting bimekizumab may be a favorable therapeutic option for r-axSpA. Differences in efficacy outcomes with bimekizumab versus ixekizumab 80 mg were mostly non-significant, depending on the populations considered.

Association of relative resection volume with patient-reported outcomes applying different levels of oncoplastic breast conserving surgery - A retrospective cohort study.

INTRODUCTION: The American Society of Breast Surgeons (ASBrS) recently classified oncoplastic breast conserving surgery (OBCS) into two levels. The association of resection ratio during OBCS with patient-reported outcomes (PRO) is unclear. MATERIALS AND METHODS: Patients with stage 0-III breast cancer undergoing OBCS between 01/2011-04/2023 at a Swiss university hospital, who completed at least one postoperative BREAST-Q PRO questionnaire were identified from a prospectively maintained institutional database. Outcomes included differences in PROs between patients after ASBrS level I (<20 % of breast tissue removed) versus level II surgery (20-50 %). RESULTS: Of 202 eligible patients, 129 (63.9 %) underwent level I OBCS, and 73 (36.1 %) level II. Six patients (3.0 %) who underwent completion mastectomy were excluded. The median time to final PROs was 25.4 months. Patients undergoing ASBrS level II surgery were more frequently affected by delayed wound healing (p < 0.001). ASBrS level was not found to independently predict any BreastQ domain. However, delayed wound healing was shown to reduce short-term physical well-being (estimated difference -26.27, 95 % confidence interval [CI] -39.33 to -13.22, p < 0.001). Higher age was associated with improved PROs. CONCLUSION: ASBrS level II surgery allows the removal of larger tumors without impairing PROs. Preventive measures for delayed wound healing and close postoperative follow-up to promptly treat wound healing disorders may avoid short-term reductions in physical well-being.

Reporting Sacroiliac Joint Imaging Performed for Known or Suspected Axial Spondyloarthritis: Assessment of SpondyloArthritis International Society Recommendations.

Whereas previous projects attempted to standardize imaging in patients with axial spondyloarthritis (axSpA), few studies have been published about the need for specific details regarding the image acquisition and lesions that may be less familiar to general radiologists. This work reports consensus recommendations developed by the Assessment of SpondyloArthritis International Society (ASAS) that aim to standardize the imaging reports in patients suspected of having or with known axSpA. A task force consisting of radiologists and rheumatologists from ASAS and one patient representative formulated two surveys that were completed by ASAS members. The results of these surveys led to the development of 10 recommendations that were endorsed by 73% (43 of 59) of ASAS members. The recommendations are targeted to the radiologist and include best practices for the inclusion of clinical information, technical details, image quality, and imaging findings in radiology reports. These recommendations also emphasize that imaging findings that indicate differential diagnoses and referral suggestions should be included in the concluding section of the radiology report. With these recommendations, ASAS aims to improve the diagnostic process and care for patients suspected of having or with known axSpA.

Estimation and probabilistic projection of age- and sex-specific mortality rates across Brazilian municipalities between 2010 and 2030.

BACKGROUND: Mortality rate estimation in small areas can be difficult due the low number of events/exposure (i.e. stochastic error). If the death records are not completed, it adds a systematic uncertainty on the mortality estimates. Previous studies in Brazil have combined demographic and statistical methods to partially overcome these issues. We estimated age- and sex-specific mortality rates for all 5,565 Brazilian municipalities in 2010 and forecasted probabilistic mortality rates and life expectancy between 2010 and 2030. METHODS: We used a combination of the Tool for Projecting Age-Specific Rates Using Linear Splines (TOPALS), Bayesian Model, Spatial Smoothing Model and an ad-hoc procedure to estimate age- and sex-specific mortality rates for all Brazilian municipalities for 2010. Then we adapted the Lee-Carter model to forecast mortality rates by age and sex in all municipalities between 2010 and 2030. RESULTS: The adjusted sex- and age-specific mortality rates for all Brazilian municipalities in 2010 reveal a distinct regional pattern, showcasing a decrease in life expectancy in less socioeconomically developed municipalities when compared to estimates without adjustments. The forecasted mortality rates indicate varying regional improvements, leading to a convergence in life expectancy at birth among small areas in Brazil. Consequently, a reduction in the variability of age at death across Brazil's municipalities was observed, with a persistent sex differential. CONCLUSION: Mortality rates at a small-area level were successfully estimated and forecasted, with associated uncertainty estimates also generated for future life tables. Our approach could be applied across countries with data quality issues to improve public policy planning.

Top-down effects of intraspeciflic predator behavioral variation.

Among-individual variation in predator traits is ubiquitous in nature. However, variation among populations in this trait variation has been seldom considered in trophic dynamics. This has left unexplored (a) to what degree does among-individual variation in predator traits regulate prey populations and (b) to what degree do these effects vary spatially. We address these questions by examining how predator among-individual variation in functional traits shapes communities across habitats of varying structural complexity, in field conditions. We manipulated Chinese mantis (Tenodera sinensis) density (six or twelve individuals) and behavioral trait variability (activity level by movement on an open field) in experimental patches of old fields with varying habitat complexity (density of plant material). Then, we quantified their impacts on lower trophic levels, specifically prey (arthropods > 4 mm) and plant biomass. Predator behavioral variability only altered prey biomass in structurally complex plots, and this effect depended on mantis density. In the plots with the highest habitat complexity and mantis density, behaviorally variable groups decreased prey biomass by 40.3%. In complex plots with low mantis densities, low levels of behavioral variability decreased prey biomass by 32.2%. Behavioral variability and low habitat complexity also changed prey community composition, namely by increasing ant biomass by 881%. Our results demonstrate that among-individual trait variation can shape species-rich prey communities. Moreover, these effects depend on both predator density and habitat complexity. Incorporating this important facet of ecological diversity revealed normally unnoticed effects of functional traits on the structure and function of food webs.

Effect of Low-Dose Aspirin on the Course of Age-Related Macular Degeneration: A Secondary Analysis of the ASPREE Randomized Clinical Trial.

Importance: Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss in old age. There is no proven intervention to prevent AMD and, apart from lifestyle, nutritional, and supplement advice, there is no intervention to delay its progression. Objective: To determine the impact of long-term low-dose aspirin on the incidence and progression of AMD. Design, Setting and Participants: The Aspirin in Reducing Events in the Elderly-AMD (ASPREE-AMD) study was an Australian-based substudy of the ASPREE trial, a multicenter, international, randomized, double-masked, placebo-clinical trial investigating the efficacy of low-dose aspirin in prolonging disability-free survival among older individuals. Retinal photography was conducted at baseline from March 2010 to January 2015, then 3 and 5 years after randomization. AMD status was determined using color retinal images and treatment records. Australian participants in ASPREE aged 70 years and older without dementia, independence-limiting physical disability, cardiovascular disease, or chronic illness limiting 5-year survival and with gradable retinal images at baseline were included. Data were analyzed from December 2022 to December 2023. Interventions: Aspirin (100 mg daily, enteric coated) or placebo. Main Outcomes and Measures: Incidence of AMD and progression from early/intermediate to late AMD. Outcomes were analyzed by modified intention-to-treat analysis. Results: A total of 4993 participants were enrolled in this substudy. Baseline characteristics were similar between groups. At the time of sponsor-determined trial termination, retinal follow-up data were available for 3208 participants, 3171 of whom were analyzed for AMD incidence and progression, with a median (IQR) age of 73.5 (71.5-76.4) years and even sex distribution (1619 [51%] female). Median (IQR) follow-up time was 3.1 (3.0-3.5) years. Cumulative AMD incidence was 195 of 1004 (19.4%) in the aspirin group and 187 of 979 (19.1%) in the placebo group (relative risk [RR], 1.02; 95% CI, 0.85-1.22; P = .86). Cumulative progression from early/intermediate AMD to late AMD was observed in 14 of 615 (2.3%) participants in the aspirin group and 18 of 573 (3.1%) in the placebo group (RR, 0.72; 95% CI, 0.36-1.44; P = .36). Conclusions and Relevance: In this trial, low-dose aspirin administered for 3 years did not affect the incidence of AMD. The evidence was weaker for progression of AMD due to low number of progressed cases. Overall, these results do not support suggestion that low-dose daily aspirin prevents the development or progression of AMD. Trial Registration: anzctr.org Identifier: ACTRN12613000755730.

Upadacitinib in Active Non-radiographic Axial Spondyloarthritis: 1-Year Data From a Double-Blind, Randomized, Placebo-Controlled, Phase 3 Trial.

OBJECTIVE: Upadacitinib improved the signs and symptoms of non-radiographic axial spondyloarthritis (nr-axSpA) versus placebo over 14 weeks in the primary analysis of the SELECT-AXIS 2 nr-axSpA study. Here, we evaluated the efficacy and safety of upadacitinib through 1 year in patients with nr-axSpA in SELECT-AXIS 2. METHODS: Patients aged at least 18 years diagnosed with nr-axSpA who fulfilled the 2009 Assessment of SpondyloArthritis International Society (ASAS) classification criteria and were receiving stable background therapy were randomized to upadacitinib 15 mg once daily or placebo for the 52-week double-blind period. Efficacy was assessed using non-responder imputation incorporating multiple imputation (NRI-MI) and as-observed analyses for binary endpoints, and mixed-effects model repeated measures for continuous endpoints. RESULTS: Of 314 randomized patients, 259 (upadacitinib, n = 129; placebo, n = 130) completed 52 weeks of treatment. More patients receiving upadacitinib versus placebo achieved ≥40% improvement in ASAS at week 52 (63% vs 43%, NRI-MI; nominal P < 0.001). Similar treatment effects were observed for the achievement of axSpA Disease Activity Score inactive disease (33% v 11%, NRI-MI; nominal P < 0.001). Overall, patients receiving upadacitinib versus placebo showed greater improvement in disease activity, inflammation, pain, function, enthesitis, and quality of life through 52 weeks. Adverse events were generally comparable between the treatment groups. No opportunistic infections, malignancies, major adverse cardiovascular events, venous thromboembolic events, inflammatory bowel disease, or deaths were reported in those receiving upadacitinib. CONCLUSION: Treatment with upadacitinib showed sustained efficacy versus placebo with no new safety findings identified through 1 year. These results support the continued favorable benefit-risk profile of upadacitinib treatment for nr-axSpA.

Axillary Surgery for Breast Cancer in 2024.

Axillary surgery for patients with breast cancer (BC) in 2024 is becoming increasingly specific, moving away from the previous 'one size fits all' radical approach. The goal is to spare morbidity whilst maintaining oncologic safety. In the upfront surgery setting, a first landmark randomized controlled trial (RCT) on the omission of any surgical axillary staging in patients with unremarkable clinical examination and axillary ultrasound showed non-inferiority to sentinel lymph node (SLN) biopsy (SLNB). The study population consisted of 87.8% postmenopausal patients with estrogen receptor-positive, human epidermal growth factor receptor 2-negative BC. Patients with clinically node-negative breast cancer and up to two positive SLNs can safely be spared axillary dissection (ALND) even in the context of mastectomy or extranodal extension. In patients enrolled in the TAXIS trial, adjuvant systemic treatment was shown to be similar with or without ALND despite the loss of staging information. After neoadjuvant chemotherapy (NACT), targeted lymph node removal with or without SLNB showed a lower false-negative rate to determine nodal pathological complete response (pCR) compared to SLNB alone. However, oncologic outcomes do not appear to differ in patients with nodal pCR determined by either one of the two concepts, according to a recently published global, retrospective, real-world study. Real-world studies generally have a lower level of evidence than RCTs, but they are feasible quickly and with a large sample size. Another global real-world study provides evidence that even patients with residual isolated tumor cells can be safely spared from ALND. In general, few indications for ALND remain. Three randomized controlled trials are ongoing for patients with clinically node-positive BC in the upfront surgery setting and residual disease after NACT. Pending the results of these trials, ALND remains indicated in these patients.

Blood Pressure Lowering in Patients With Central Hypertension: A Randomized Clinical Trial.

BACKGROUND: Cuff blood pressure (BP) is recommended for guiding hypertension management. However, central BP has been proposed as a superior clinical measurement. This study aimed to determine whether controlling hypertension as measured by central BP was beneficial in reducing left ventricular mass index beyond control of standard cuff hypertension. METHODS: This multicenter, open-label, blinded-end point trial was conducted in individuals treated for uncomplicated hypertension with controlled cuff BP (<140/90 mm Hg) but elevated central BP (≥0.5 SD above age- and sex-specific normal values). Participants were randomized to 24-months intervention with spironolactone 25 mg/day (n=148) or usual care control (n=153). The primary outcome was change in left ventricular mass index measured by cardiac MRI. Cuff and central BPs were measured by clinic, 7-day home and 24-hour ambulatory BPs. RESULTS: At 24-months, there was a greater reduction in left ventricular mass index (-3.2 [95% CI, -5.0 to -1.3] g/m2; P=0.001) with intervention compared with control. Cuff and central BPs were lowered by a similar magnitude across all BP measurement modes (eg, clinic cuff systolic BP, -6.16 [-9.60 to -2.72] mm Hg and clinic central systolic BP, -4.96 [-8.06 to -1.86] mm Hg; P≥0.48 all). Secondary analyses found that changes in left ventricular mass index correlated to changes in BP, with the magnitude of effect nearly identical for BP measured by cuff (eg, 24-hour systolic BP, ß, 0.17 [0.02-0.31] g/m2) or centrally (24-hour systolic BP, ß, 0.16 [0.01-0.32] g/m2). CONCLUSIONS: Among individuals with central hypertension, spironolactone had beneficial effects in reducing LV mass. Secondary analyses showed that changes in LV mass were equally well associated with lower measured standard cuff BP and central BP. REGISTRATION: URL: https://www.anzctr.org.au/; Unique identifier: ACTRN12613000053729.

Exploring the Effects of Ixekizumab on Pain in Patients with Ankylosing Spondylitis Based on Objective Measures of Inflammation: Post Hoc Analysis from a Large Randomized Clinical Trial.

INTRODUCTION: The objective of this analysis is to evaluate the improvement in spinal pain with ixekizumab, placebo, and adalimumab based on objective measures of inflammation response in patients with ankylosing spondylitis (AS). METHODS: The COAST-V 52-week, double-blind, placebo-controlled, randomized phase III trial examined the efficacy of ixekizumab in patients with active AS; adalimumab was used as an active reference arm. Treatment effects on reduction in pain were assessed by objective measures of controlled and persisting inflammation (defined by magnetic resonance imaging [MRI], C-reactive protein [CRP], or MRI + CRP status). Pathway analysis was used to analyze treatment effect that was not attributable to reduction in inflammation biomarkers. RESULTS: In patients with AS, when inflammation was controlled as assessed by MRI, patients treated with ixekizumab experienced a reduction in spinal pain at night (SP-N, numeric rating scale, ixekizumab mean = - 3.9, p < 0.001, adalimumab mean = - 2.6, p < 0.05) compared to placebo (mean = - 1.6) at week 16. When inflammation was controlled as assessed by MRI + CRP, ixekizumab and adalimumab had numerically greater reductions at week 16 in SP-N versus placebo. All ixekizumab groups had further improvements at week 52. When inflammation was persisting as assessed by MRI + CRP, ixekizumab-treated patients had significant reduction in SP-N (mean = - 3.7, p < 0.001) versus placebo (mean = - 1.7), improvement with adalimumab did not reach significance (mean = - 2.6, p = 0.06). In the pathway analysis at week 16, ixekizumab had a greater effect on pain outcomes compared to adalimumab. CONCLUSION: This post hoc analysis is supportive of the hypothesis that ixekizumab reduces pain in AS by additional mechanisms other than the reduction of measurable inflammation. TRIAL REGISTRATION NUMBER: NCT02696785.

Adding ultrasound to treat-to-target shows no benefit in achieving clinical remission nor in slowing radiographic progression in rheumatoid arthritis: results from a multicenter prospective cohort.

OBJECTIVE: To assess whether using ultrasound (US) in addition to clinical information versus only clinical information in a treat-to-target (T2T) strategy leads to more clinical remission and to less radiographic progression in RA. METHODS: Patients with RA from the 2-year prospective BIODAM cohort were included. Clinical and US data (US7-score) were collected every 3 months and hands and feet radiographs every 6 months. At each visit, it was decided whether patients were treated according to the clinical definition of T2T with DAS44 remission as benchmark (T2T-DAS44). T2T-DAS44 was correctly applied if: (i) DAS44 remission had been achieved or (ii) if not, treatment was intensified. A T2T strategy also considering US data (T2T-DAS44-US) was correctly applied if: (i) both DAS44 and US remission (synovitis-score < 2, Doppler-score = 0) were present; or (ii) if not, treatment was intensified. The effect of T2T-DAS44-US on attaining clinical remission and on change in Sharp-van der Heijde score compared to T2T-DAS44 was analysed. RESULTS: A total of 1016 visits of 128 patients were included. T2T-DAS44 was correctly followed in 24% of visits and T2T-DAS44-US in 41%. DAS44 < 1.6 was achieved in 39% of visits. Compared to T2T-DAS44, using the T2T-DAS44-US strategy resulted in a 41% lower likelihood of DAS44 remission [OR (95% CI): 0.59 (0.40;0.87)] and had no effect on radiographic progression [ß(95% CI): 0.11 (- 0.16;0.39)] assessed at various intervals up to 12 months later. CONCLUSION: Our results do not suggest a benefit of using the US7-score in addition to clinical information as a T2T benchmark compared to clinical information alone. Key Points • Ultrasound has a valuable role in diagnostic evaluation of rheumatoid arthritis, but it is unclear whether adding ultrasound to the clinical assessment in a treat-to-target (T2T) strategy leads to more patients achieving remission and reduction in radiographic progression. • Our data from a real-world study demonstrated that adding information from ultrasound to the clinical assessment in a T2T strategy led to a lower rather than a higher likelihood of obtaining clinical remission as compared to using only clinical assessment. • Our data demonstrated that adding ultrasound data to a T2T strategy based only on clinical assessment did not offer additional protection against radiographic progression in patients with RA. • Adding US to a T2T strategy based on clinical assessment led to far more treatment intensifications (with consequences for costs and exposure to adverse events) without yielding a meaningful clinical benefit.