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BACKGROUND: Paced QRS morphology may vary during left bundle branch area pacing (LBBAP) as per the pacing location. It remains unclear whether electrocardiographic changes observed during LBBAP can predict clinical outcomes. OBJECTIVE: To assess correlation between characteristics of paced QRS on electrocardiogram and clinical outcomes in heart failure (HF) patients with non-ischemic cardiomyopathy. METHODS: Of 79 consecutive HF patients receiving LBBAP, 59 patients were included in this prospective study after exclusions. LBBAP was performed using Medtronic 3830 lead. Patients were categorized into various groups based on paced QRS morphology in lead V1 (qR and Qr), QRS axis (normal, left or right) and V6 R wave peak time (RWPT, ≤80 or >80 ms) to compare echocardiographic outcomes. RESULTS: RWPT was significantly shorter (75.7±17.5 vs 85.3±11.3 ms, P=0.014), transition during threshold test more commonly observed (81.5% vs 53%, P=0.02) and improvement in left ventricular ejection fraction (LVEF) was significantly greater in qR group (21.4±6.4 vs 16.4±8.3%, P=0.013) compared to Qr group. RWPT or LVEF did not differ in patients with different paced QRS axis (P>0.05). While qR morphology and presence of transition during threshold test independently predicted LVEF improvement, RWPT lacked predictive value. Non-responders had greater incidence of loss of 'R' prime (P=0.009) and prolonged RWPT (P=0.003) on follow up compared to average and super-responders. CONCLUSIONS: Paced qR morphology and transition during threshold test predicted greater improvement in LVEF while RWPT lacked predictive value. Loss of terminal 'R' in lead V1 and prolongation of RWPT on follow up prognosticated non-response to LBBAP.

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OBJECTIVE: Radiographic assessment of sacroiliac joints (SIJs) according to the modified New York (mNY) criteria is key in classification of axSpA but has moderate inter-reader agreement. We aimed to investigate the reliability improvements scoring SIJ radiographs after applying an online real-time iterative calibration (RETIC) module, in addition to a slideshow and video alone. METHODS: Nineteen readers, randomized to 2 groups (A/B), completed 3 calibration steps: I) review of manuscripts, II) review of slideshow and video and group A completed RETIC, III) re-review of slideshow+video and group B completed RETIC . The RETIC module gave instant feedback on reader's gradings and continued until predefined reliability (kappa) targets for mNY positivity/negativity were met. Each step was followed by scoring different batches of 25 radiographs (Exercises I-III). Agreement (kappa) with an expert radiologist was assessed for mNY+/mNY- and individual lesions. Improvements by training strategies were tested by linear mixed models. RESULTS: In exercises I/II/III, mNY kappas were 0.61/0.76/0.84 in group A, and 0.70/0.68/0.86 in group B, respectively, i.e. increasing, mainly after RETIC completion. Improvements were observed for both grading mNY+/mNY- and for individual pathologies, both in experienced and, particularly, inexperienced readers. Completion of the RETIC module in addition to slideshow and video caused a significant kappa increase of 0.17 (CI: 0.07-0.27, P=0.002) for mNY+/mNY- grading, while completion of slideshow and video alone did not (0.0; CI -0.10-+0.10, P=0.99). CONCLUSION: Agreement on scoring radiographs according to the mNY criteria significantly improved when adding an online RETIC module, but not by slideshow and video alone.

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BACKGROUND: Along bacteria, yeasts are common in forages and forage fermentations as spoilage microbes or as additives, yet few studies exist with species-level data on these fungi's occurrence in feedstuff. Active dry yeast and other yeast-based products are also common feed additives in animal husbandry. Here, we aimed to characterize both fermented and non-fermented milking cow feedstuff samples from Hungary to assess their microbial diversity in the first such study from Central Europe. RESULTS: We applied long-read bacterial metabarcoding to 10 fermented and 25 non-fermented types of samples to assess bacterial communities and their characteristics, surveyed culturable mold and yeast abundance, and identified culturable yeast species. Fermented forages showed the abundance of Aerococcaceae, Bacillaceae, Brucellaceae, Lactobacillaceae, Staphylococcaceae, and Thermoactinomycetaceae, non-fermented ones had Cyanothecaceae, Enterobacteriaceae, Erwiniaceae, Gomontiellaceae, Oxalobacteraceae, Rhodobiaceae, Rickettsiaceae, and Staphylococcaceae. Abundances of bacterial families showed mostly weak correlation with yeast CFU numbers, only Microcoleaceae (positive) and Enterococcaceae and Alcaligenaceae (negative correlation) showed moderate correlation. We identified 14 yeast species, most commonly Diutina rugosa, Pichia fermentans, P. kudriavzevii, and Wickerhahomyces anomalus. We recorded S. cerevisiae isolates only from animal feed mixes with added active dry yeast, while the species was completely absent from fermented forages. The S. cerevisiae isolates showed high genetic uniformity. CONCLUSION: Our results show that both fermented and non-fermented forages harbor diverse bacterial microbiota, with higher alpha diversity in the latter. The bacterial microbiome had an overall weak correlation with yeast abundance, but yeasts were present in the majority of the samples, including four new records for forages as a habitat for yeasts. Yeasts in forages mostly represented common species including opportunistic pathogens, along with a single strain of Saccharomyces used as a feed mix additive.

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Among the challenges in delivering integrated health and social care services is the need to attend to the coordination of tasks, roles, activities, and operations, while considering how these efforts are experienced by patients, carers and communities. The literature has noted an important disconnect between how providers and leaders view their efforts to coordinate service delivery, and how patients perceive these efforts on the receiving end. Our team has provided guidance to integrated care efforts in Ontario, Canada by drawing on Goffman's theory of Dramaturgy to help classify the actions of integrated care delivery as linked to the roles individuals play in the delivery of care. Using this framing helps to uncover how "backstage" processes (such as team-functioning, funding models, and digital infrastructures) create a necessary foundation on which "frontstage" actions (or performances) can be effectively delivered.

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INTRODUCTION: Pain in both peripheral and axial joints is a major symptom in patients with psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA). Emerging evidence demonstrates pain mechanisms, beyond those related to inflammation or joint damage, based on aberrant processing of nociceptive stimuli peripherally as well as centrally. The Janus kinase/signal transducers and activators of transcription (JAK-STAT) signaling pathway has been implicated in the processing of pain beyond its role in mediating inflammation and inhibitors of this pathway approved for the treatment of axSpA and PsA have been shown to alleviate a broad array of pain outcomes in both axial and peripheral joints. AREAS COVERED: We review recent definitions and standardization of the nomenclature for categorizing chronic pain according to causality, assessment tools to evaluate nociplastic pain, the pathophysiologic role of JAK-STAT signaling in nociplastic pain, evidence for the presence of nociplastic pain in axSpA and PsA, and the impact of JAK inhibitors (JAKi) on pain outcomes in clinical trials (PubMed: 01/01/2019-04/01-2024). EXPERT OPINION: Nociplastic pain assessment has been confined almost entirely to the use of a limited number of questionnaires in cross-sectional studies of these diseases. Though effective for alleviating pain, it is unclear if JAKi specifically impact nociplastic pain.

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BACKGROUND: Obesity is associated with adverse cardiac remodeling and is a key driver for the development and progression of heart failure (HF). Once-weekly semaglutide (2.4 mg) has been shown to improve HF-related symptoms and physical limitations, body weight, and exercise function in patients with obesity-related heart failure with preserved ejection fraction (HFpEF), but the effects of semaglutide on cardiac structure and function in this population remain unknown. OBJECTIVES: In this echocardiography substudy of the STEP-HFpEF Program, we evaluated treatment effects of once-weekly semaglutide (2.4 mg) vs placebo on cardiac structure and function. METHODS: Echocardiography at randomization and 52 weeks was performed in 491 of 1,145 participants (43%) in the STEP-HFpEF Program (pooled STEP-HFpEF [Semaglutide Treatment Effect in People with Obesity and HFpEF] and STEP-HFpEF DM [Semaglutide Treatment Effect in People with Obesity, HFpEF, and Type 2 Diabetes] trials). The prespecified primary outcome was change in left atrial (LA) volume, with changes in other echocardiography parameters evaluated as secondary outcomes. Treatment effects of semaglutide vs placebo were assessed using analysis of covariance stratified by trial and body mass index, with adjustment for baseline parameter values. RESULTS: Overall, baseline clinical and echocardiographic characteristics were balanced among those receiving semaglutide (n = 253) and placebo (n = 238). Between baseline and 52 weeks, semaglutide attenuated progression of LA remodeling (estimated mean difference [EMD] in LA volume, -6.13 mL; 95% CI: -9.85 to -2.41 mL; P = 0.0013) and right ventricular (RV) enlargement (EMD in RV end-diastolic area: -1.99 cm2; 95% CI: -3.60 to -0.38 cm2; P = 0.016; EMD in RV end-systolic area: -1.41 cm2; 95% CI: -2.42 to -0.40] cm2; P = 0.0064) compared with placebo. Semaglutide additionally improved E-wave velocity (EMD: -5.63 cm/s; 95% CI: -9.42 to -1.84 cm/s; P = 0.0037), E/A (early/late mitral inflow velocity) ratio (EMD: -0.14; 95% CI: -0.24 to -0.04; P = 0.0075), and E/e' (early mitral inflow velocity/early diastolic mitral annular velocity) average (EMD: -0.79; 95% CI: -1.60 to 0.01; P = 0.05). These associations were not modified by diabetes or atrial fibrillation status. Semaglutide did not significantly affect left ventricular dimensions, mass, or systolic function. Greater weight loss with semaglutide was associated with greater reduction in LA volume (Pinteraction = 0.033) but not with changes in E-wave velocity, E/e' average, or RV end-diastolic area. CONCLUSIONS: In the STEP-HFpEF Program echocardiography substudy, semaglutide appeared to improve adverse cardiac remodeling compared with placebo, further suggesting that treatment with semaglutide may be disease modifying among patients with obesity-related HFpEF. (Research Study to Investigate How Well Semaglutide Works in People Living With Heart Failure and Obesity [STEP-HFpEF]; NCT04788511; Research Study to Look at How Well Semaglutide Works in People Living With Heart Failure, Obesity and Type 2 Diabetes [STEP-HFpEF DM]; NCT04916470).

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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