In total hip arthroplasty, stem alignment has been proposed to occur in the neutral and flexed positions. Nonetheless, there is a paucity of research on the relationship between the shape of the medullary cavity cross-section and its compatibility with the stem shape. A total of 216 female (Asian) patients with no history of fracture or surgery on the contralateral side with complete computed tomography (CT) data were included in the study. The plane of the medullary cavity in the neutral (N group) and flexion (F group) alignments was defined. The ratio of the plane of medullary cavity widths at 80mm and 130mm distal from the center of the femoral head in these two medullary cavity planes was defined as the modified canal flare index (mCFI). The mCFI was used to assess the compatibility between the configuration of the medullary canal plane and that of the stem. All patients in the N group formed a plane, whereas 58 patients in the F group (26.9%) lacked a clear calcar femorale. Fifteen patients in the F group (9.4%) were excluded because of the inability to insert the stem, leaving 143 patients in the F group. The mean mCFI was significantly lower in the F group (0.692 ± 0.128) than in the N group (0.807 ± 0.073). The mCFI values of frequently used stems were all close to the mCFI of flexion alignment. The medullary cavity shape differed in the neutral and flexion alignments. Preoperative three-dimensional planning is helpful because the flexion alignment may not allow for the insertion of an optimally sized stem.

Cementless femoral stem in arthroplasty for hip fracture: Early radiological subsidence at 3 months and predictive factor out of 117 cases.

To evaluate the characteristics and their change trends of major radiographic parameters of hips in axial spondyloarthritis (axSpA) patients with end-stage hip involvement from a single high-volume tertiary center over a 24-year period. Between 2001 and 2024, the radiographic trends of hips in axSpA patients with end-stage hip involvement were retrospectively reviewed. These radiographic parameters included bony ankylosis, acetabular protrusio, dislocation, obturator foramen ratio (OFR), canal flare index (CFI) and neck shaft angle (NSA). The baseline demographic, disease-related and laboratory parameters before surgery were also collected. Trend analyses over the study period were assessed using the Jonkheere-Terpstra trend test or the Cochran-Armitage trend test for clinical and radiographic parameters. All the joints were divided into the 2001-2012 group and 2013-2024 group according to the year of surgery, and the intergroup comparisons were conducted to further elucidate temporal changes. The overall incidence of bony ankylosis, acetabular protrusio and dislocation before operation were 40.2%, 14.8% and 9.8%, respectively. The median value of OFR, CFI and NSA were 1.5 (1.2, 1.7), 3.2 (2.6, 3.8) and 141.0° (135.0°, 148.0°), respectively. Notably, only the value of OFR demonstrated increasing trend (P=0.001) among these radiographic parameters of hip, although some clinical parameters demonstrated increasing trend [hemoglobin (Hb) (P < 0.001), albumin (ALB) (P < 0.001), short form 12-item health survey (SF-12) physical component summary (PCS) (P=0.005), Harris hip score (HHS) (P=0.003)] or decreasing trend [erythrocyte sedimentation rate (ESR) (P < 0.001), C-reactive protein (CRP) (P < 0.001), Bath ankylosing spondylitis disease activity index (BASDAI) (P=0.013), Bath ankylosing spondylitis functional index (BASFI) (P < 0.001)]. The results of intergroup comparisons between 2001-2012 inpatient group (n=421) and 2013-2024 inpatient group (n=577) showed that no significant differences were found for these radiographic parameters of hip, although some clinical parameters were significantly different, including gender (P=0.004), body mass index (BMI) (P=0.002), age at disease onset (P < 0.001) and HHS (P < 0.001). The radiographic parameters of hip in axSpA patients with end-stage hip involvement did not show a trend of improvement over time, despite observed improvements in disease activity control and functional status. This dissociation between clinical improvement and persistent structural damage presents considerable technical challenges for subsequent surgical reconstruction with total hip arthroplasty.

To determine whether radiographic templating of femoral stem size for total hip arthroplasty (THA) using extended and flexed hip radiographs are interchangeable. Retrospective radiographic study. A total of 25 dogs evaluated as THA candidates. Hip-extended and hip-flexed radiographs were templated for femoral stem implant size by three surgeons. A fourth investigator measured femoral length, canal flare index (CFI), and osteoarthritis scores for each projection and recorded implant size from surgical records. Templated stem sizes from each projection were compared with the implanted stem sizes using Bland-Altman analysis. Descriptive statistics were reported based on data distribution. Templated femoral stem size differed between surgeons (p = .014); the median (IQR) stem size was #9 (8-10) for one surgeon, compared to #8 (7-9) for the other surgeons. Templated stem sizes on extended and flexed radiographs were #8 (7-9) and #9 (7-9), respectively (p < .0001). The mean (SD) CFI in extended and flexed projections were 1.61 (0.21) and 1.89 (0.30), respectively (p < .0001). Implant size was underestimated using the extended projection (mean difference: -0.54) and overestimated using the flexed projection (mean difference: 0.30). Positive proportional bias was present between the extended and flexed projections (slopes: 0.22 and 0.25; p < .003). Neither templating method consistently predicted the clinical femoral stem implant size. Hip-flexed templating may serve as a practical alternative when extended projections are not possible, though intraoperative assessment remains essential for final implant selection, particularly since measurement bias increased for stems larger than size 9.

Background. The most recent literature regarding the discontinuation of immunosuppressive therapy (IS) in patients with systemic lupus erythematosus (SLE) in remission highlights that approximately one in four patients experience a relapse. We have learned how flare-ups impact the extent of accumulated damage, caused on the one hand by disease activity and on the other by prolonged exposure to IS therapy. This clearly supports the need for a tool that guides clinicians towards safe management of therapy in patients in remission. We therefore evaluated several serological biomarkers, such as anti-native DNA, C3, C4, anti-C1q, anti-PTX3, APRIL, BLyS, C3a and C3c. Based on the results observed, we created an algorithm capable of estimating the risk of relapse in patients in remission following the discontinuation of IS therapy. Materials and methods. We conducted a retrospective study of 57 patients with SLE who had discontinued IS therapy after achieving remission. Clinical SLEDAI-2K = 0, associated with stable background therapy and/or a prednisone dose ≤5 mg/day, identified remission status. Flares were defined according to the SLEDAI-Flare-Index. A multivariate logistic regression model was applied to evaluate the association between the risk of flare and clinical and serological data collected in the 6 months following discontinuation of IS therapy. The variables found to be significant were then combined to create a flare predictor algorithm. Results. Fifteen patients (26.3%) experienced a relapse, on average 4.35 (± 4.1) years after discontinuation of IS therapy. Serum BLyS levels were significantly higher in patients with relapse (median 0.869 ng/mL, IQR 0.669–1.262; p = 0.033) than in patients who remained in remission. Maintenance therapy with hydroxychloroquine (HCQ) at the time of IS therapy discontinuation showed a protective effect (OR = 0.21; p = 0.019). BLyS values, native anti-DNA antibody positivity, remission greater than 3 years at the time of IS therapy discontinuation, and HCQ use, weighted as shown in Figure 1, provided the optimal combination for constructing a flare prediction algorithm (AUC = 0.779; SE = 100%; SP = 62.9%). All patients who experienced a flare-up had a BLys Lupus Flare Index (BLyFI) value greater than the cut-off of -3.43. Conclusions. Through the combination of serum BLyS levels with other variables readily available in clinical practice, we have developed a non-invasive tool capable of predicting the risk of relapse in patients in remission candidates for discontinuation of immunosuppressive therapy.

Background. Pregnancy in systemic lupus erythematosus (SLE) is associated with increased risk of fetal and maternal complications, as well as a higher risk of disease flares. Data on pregnancy’s impact on damage accrual in SLE are limited. We aimed to assess the role of pregnancy and related factors in damage increase in SLE patients. Methods. Consecutive patients fulfilling the 2019-ACR/EULAR SLE criteria were prospectively enrolled at pregnancy detection and monitored every 4 weeks at two referral centers. At baseline, demographic, clinical, and treatment data were collected. Disease activity was assessed by SLE Disease Activity Index-2k score(SLEDAI-2k); flares during pregnancy by the modified SELENA-SLEDAI flare index. Remission was defined by DORIS-criteria, and low disease activity state (LLDAS) by the Asian Pacific definition. Disease was defined as active if SLEDAI-2K&gt;4. Pregnancy outcomes included preeclampsia, premature membrane rupture &lt;37 gestational-weeks, small for gestational-age, intrauterine growth restriction, intrauterine fetal death and birthweight &lt;2500 gr. Damage accumulation was assessed using the SLICC Damage Index score over two years pre-pregnancy, one year pre- and one year post-pregnancy. Factors influencing damage accrual during pregnancy were analyzed by logistic regression. To assess the effect of pregnancy per se on damage accrual, we examined this relationship using a cross-over design. The year before pregnancy was compared with the year post-pregnancy in terms of damage accrual; results are expressed as delta damage. Results. We analyzed 165 pregnancies in 122 patients. Figure1 shows demographic, clinical, and serological features; Figure2 reports obstetric outcomes and first pregnancy visit data. At conception, 26 pregnancies(15.8%) had pre-existing damage(mean 1.1, SD±0.32). In the year after pregnancy, 29 cases (17.6%) had a SLICC score of 1 or higher(mean 1.24, SD ±0.51), including 3 new damage cases in previously unaffected patients. 7 patients (4.4%) presented increased damage post-pregnancy, consisting of osteoporotic fracture, malignancy, cerebrovascular event, scarring alopecia, cognitive impairment, and diabetes mellitus. Only 1 new damage event(cataract) occurred in the year before pregnancy. At logistic regression of the cross-over analysis, pregnancy per se was not significantly associated with SLICC increase (OR 3.61, 95% CI). Exploring variables potentially associated with damage accrual, with a multivariate logistic regression analysis we found that pre-existing organ damage (OR 8.24, 95% CI) and disease activity at the beginning of pregnancy (OR 6.65, 95% CI) were independently associated with post-pregnancy damage accrual. No associations emerged with age, disease duration, overlap syndromes, or ongoing therapies during pregnancy. Conclusions. In SLE patients followed at tertiary centers, pregnancy per se was not linked to damage accrual. However, in patients with pre-existing damage and active disease at conception, damage accrual should be considered in the pre-conceptional counselling. These results highlight the need for organ damage prevention strategies and pregnancy planning during disease control

Abstract Accurate prediction of solar flares is essential for space weather warnings and safeguarding technological infrastructure. This study proposes a dual-stage flare prediction framework leveraging the full-disk flare index (FI). In the first stage, FI is decomposed into long-term trend and short-term disturbance components via a “trend-disturbance” decomposition strategy. The iTransformer model independently forecasts each component, which is then fused to generate high-fidelity FI predictions. The second stage develops a regression-classification architecture that maps predicted FI values to flare intensity levels, enabling comprehensive full-disk flare forecasting. Experimental results indicate that the decomposition strategy improves performance across all flare classes, reducing the mean absolute error of FI prediction to 19.066 and achieving a TSS of 0.639 and an F1 score of 0.649 for M-class flares. Tested from the solar minimum in 2019 through the 2024 solar maximum, the framework surpasses the operational forecasting capabilities of leading space weather prediction centers such as SWPC and SEPC, successfully delivering reliable 72 hr flare warnings during 2024 May events. The dual-stage framework introduces an innovative approach to improving the accuracy and reliability of flare prediction, offering a valuable reference for forecasting extreme solar activity events.

Proximal femoral medullary canal morphology is a key determinant of cementless stem fit, primary stability, and load transfer in total hip arthroplasty (THA), yet population-level three-dimensional characterization remains limited. This study was designed to quantify variability in canal geometry and to capture dominant anatomical modes of variation with statistical shape modeling (SSM). Computed tomography data from 763 candidates for primary THA (389 female, 374 male; 20-92 years) were analyzed. Endosteal contours of the proximal canal were processed to build a point-correspondent SSM by principal component analysis (PCA). Five geometric features were evaluated per specimen: equivalent radius (normalized), roundness, major-axis angle (torsion), flare index, and curvature. Substantial inter-individual variability was observed across all features, with differences by sex and age. The first three principal components accounted for 68.4% of total variance, and each showed interpretable associations with at least one geometric feature. Model behavior was examined by synthetic sampling within ±2 SD (specificity) and by 10-fold cross-validation (generalization), indicating faithful reconstruction of real shapes and stable performance on held-out data. These findings provide a compact description of proximal canal shape variation and its key geometric drivers. The resulting population map is expected to support implant selection and sizing in preoperative planning, inform shape-based classification, and guide design envelopes for standard and personalized stems, with potential efficiencies in manufacturing and material use.

Abstract A new daily composite of the solar flare index (SFI) and the hemispherically‐resolved versions (hSFI) are presented for 1937 to 2024. The data set confirms that the northern hemisphere (NH) dominated solar flare activity during Solar Cycles 17 to 21, but that the southern hemisphere has dominated from Solar Cycle 22 to present. That said, the highest SFI value occurred in the NH during the recent superstorm of May 2024. In sunspot activity, the “Gnevyshev‐Ohl rule” shows that the sum of sunspot numbers during even‐numbered cycles is related to those of adjacent odd‐numbered cycles. A similar rule appears to apply to SFI. The “Gnevyshev gap” phenomenon where solar maximum activity sometimes has two peaks separated by up to 1–2 years of a gap is confirmed for SFI. Although our data set represents the longest continuous daily data set for solar flare activity to‐date, it is known that stronger solar flare events occurred before 1937. Therefore, a brief discussion of earlier solar flare events in the historical record is also provided for context. The statistics of the SFI and hSFI series are compared to other solar and geomagnetic activity indices, including the May and October 2024 solar storms. Statistical analysis of past geomagnetic storms confirms they are more frequent during active cycles and less frequent during solar minima. Strong geomagnetic storms are also more likely to occur during the positive phase of a 1.7 year's quasi‐biennial oscillation in solar activity. The likelihood of low‐magnetic latitude aurorae seems to have a 30 year periodicity component.

The proximal femur morphology changes with age, which may complicate the compatibility of contemporary cementless stem designs in very elderly patients. This study investigated the internal and external proximal femur morphology, correlated canal dimensions with external dimensions, and examined whether age-associated changes in the femoral canal and external morphology are related in subjects aged 80 years and older. Three-dimensional models of human femora were reconstructed from computed tomographic (CT) scans of 90 very elderly subjects (mean 84 years, range 80-105 years). Morphological parameters describing the location of the femoral head center (FHC) (i.e. neck-shaft angle [NSA], mediolateral offset [ML-offset], and distance between lesser trochanter (LT) and FHC [LT-FHC]) and parameters describing the canal morphology (i.e. the cortices, canal dimensions, and canal flare index [CFI]) were measured. Regression and correlation analyses were performed in order to assess the relation between internal and external morphology. No significant associations regarding dimensions nor geometry between internal and external femur morphology could be detected. Canal dimensions were not able to predict the external dimensions more accurately than the deviation between the individual value and the mean value for the total cohort. Based on these findings, proportional sizing of the cementless femoral component is not necessarily endorsed in very elderly patients, and age-associated changes of the femoral canal and external morphology do not appear to be related. However, further research is needed to evaluate the ability of contemporary non-modular cementless stems to anatomically reconstruct the proximal femur in very elderly patients specifically.

Background:Intraoperative fractures are a significant complication of bipolar hemiarthroplasty for hip fractures in older patients. Femoral geometry classified as Dorr C is associated with a high risk of intraoperative fractures when a cementless stem is used. However, the impact of the duration from injury to surgery on the risk of intraoperative fractures remains unclear. We hypothesized that a prolonged duration from injury to surgery increases the likelihood of intraoperative fractures. The aim of this study was to evaluate the relationship between the duration from injury to surgery and the occurrence of intraoperative fractures.Methods:This case-control study analyzed 548 patients who underwent bipolar hemiarthroplasty for hip fractures at 2 hospitals between April 2017 and March 2024. The patients were categorized into 2 groups based on the occurrence of intraoperative fractures: the “intraoperative fracture (+) group” and “intraoperative fracture (−) group.” The relationship between intraoperative fractures and the duration from injury to surgery was assessed.Results:Intraoperative fractures occurred in 37 of 548 cases. The duration from injury to surgery was 6.05 and 3.56 days in the intraoperative fracture (+) and (−) groups, respectively (p = 0.002). The canal flare index (CFI) was 3.30 and 3.73 in the intraoperative fracture (+) and (−) groups, respectively (p < 0.001). Logistic regression analysis revealed that the regression coefficient for the duration from injury to surgery was 0.04 (p = 0.04), and for CFI −1.09 (p < 0.001), both associated with an increased risk of intraoperative fracture. In patients with intraoperative fractures, an investigation into delays in surgery beyond 48 hours showed that more than half of these delays were due to hospital-related concerns.Conclusions:Intraoperative fractures increase with the CFI and duration from injury to surgery. In some cases, medical facilities may be able to reduce this duration. To minimize the risk of intraoperative fractures in bipolar hemiarthroplasty for older patients, reduction of the duration from injury to surgery is essential.Level of Evidence:Level III, Case-control study. See Instructions for Authors for a complete description of levels of evidence.

Total hip arthroplasty (THA) is the most effective surgical intervention for end-stage hip diseases, yet approximately 10-15% of patients require revision surgery due to biomechanical complications such as stress shielding and aseptic loosening. These complications stem from mechanical environment mismatch between implants and host bone, while patients exhibit substantial inter-individual variations in skeletal geometry and bone quality that standard implants cannot accommodate. This study proposes an innovative "3D Printing-Neural Network Co-modelling" (3PNN) framework to enable patient-specific preoperative biomechanical prediction and implant design optimization. First, we developed a biomimetic bone matrix material with tunable mechanical properties, achieving elastic modulus spanning the complete range from cancellous to cortical bone (0.1-20 GPa). Second, based on five key geometric descriptors (neck-shaft angle, acetabular inclination, femoral anteversion, canal flare index, and cortical thickness index), we established a parametric pelvis-femur model and generated 95 models covering patient diversity through Latin hypercube sampling. Subsequently, we fabricated this biomimetic bone model library using multi-material 3D printing and measured stress distributions after standard prosthesis implantation via digital image correlation (DIC), acquiring 120 high-quality experimental datasets. Based on these data, we trained a bidirectional 3PNN machine learning framework: Forward-3PNN rapidly predicts stress distribution from geometric parameters (R²=0.89, MAPE=9.2%), while Inverse-3PNN inversely infers bone quality from mechanical response (r=0.87 vs DXA). Parametric sensitivity analysis revealed that neck-shaft angle and canal flare index are the most critical factors influencing stress distribution. In validation with 42 retrospective clinical cases, this framework successfully guided personalized implant selection and identified high-risk patients. By integrating the fidelity of physical models with the efficiency of machine learning, this study provides a novel paradigm for personalized medical device design and digital twin healthcare systems, demonstrating significant clinical translational value and design innovation insights.

PV222 / #475Poster Topic:AS23 - SLE-Diagnosis, Manifestations, &amp; OutcomesBackground/Purposeto identify and compare different phenotypes of severe flares in a monocentric cohort of SLE patients.MethodsThis is a retrospective study of prospectively collected data from a monocentric cohort of adult SLE patients (2019 EULAR-ACR classification criteria), hospitalized in the last 5 years, due to a severe flare (SELENA-SLEDAI flare index definition). Patients with concomitant infections, oncologic and onco-hematologic conditions were excluded. Hospitalization was defined as baseline (t0). At t0 demographics, clinical, laboratory and treatment data were collected. Disease activity was assessed with SLEDAI-2K and BILAG-2004. Disease outcomes (Lupus Low Disease Activity State (LLDAS) and DORIS remission) and treatment were evaluated at 3, 6, 12-months (t3, t6, t12) after the flare. Organ damage (SLICC Damage Index (SLICC-DI)) was assessed at baseline and t12. A clustering analysis was performed on SLE flares, with a hierarchical method. Post hoc elaborations (1-way analysis of variance with Bonferroni test for quantitative variables, and Chi-square test for qualitative variables) were performed to estimate any statistically significant differences between the clusters.Results122 severe flares in 110 patients (female 83%, Caucasian 89%) were included. 3 clusters were identified, composed of 40, 34 and 48 flares respectively.Cluster 1included flares that occurred in younger patients (mean age 38.2±12 vs 46.3±13.9 and 43.2±11.1 inclusters 2 and 3respectively; p=0.007) with a shorter disease duration (9.1±6 years vs 17.5±11.5 and 15±8.7; p=0.0001), characterized by a higher frequency of BILAG A manifestations in the constitutional, cardiopulmonary and musculoskeletal domains (p= 0.0001). These flares presentedhyperinflammatorystigmata (higher C-reactive protein, more severe lymphopenia, a tendency for higher ferritin values) and a richer autoantibody profile (anti-dsDNA, anti-Smith, anti-nucleosome, anti-hystone), compared to the other clusters.Cluster 2included less severe flares with more BILAG B scores (59% vs 28% and 19%; p=0.0001) and mainly joint and skin manifestations.Cluster 3was characterized by a clear predominance of renal flares (96%) (p=0.0001). 85% of flares in each cluster required adding/changing the immunsuppressant, mainly Mycophenolate in clusters 1and3(30% and 47% vs 9%; p=0.001). Glucocorticoid pulses were less frequently used in cluster 2, accordingly to a milder flare phenotype (15% vs 50% and 83%; p= 0.0001). Belimumab was added in 25% and 30% of flares in cluster 1and2respectively, only in 8.5% in cluster 3(p=0.02), as the majority of flares occurred before the approval of Belimumab for lupus nephritis. At t6 and t12, flares inclusters 1and3presented a significantly higher cumulative glucocorticoid dose, compared tocluster 2. At the different timepoints, cluster 1and3presented a comparable and quite low percentage of patients that achieved LLDAS and remission (Table 1). No differences emerged among the clusters for SLICC-DI at t12.Table 1.*Cluster 2 vs 1 and 3Conclusionsdifferent phenotypes of severe SLE flares exist. We identified a “hyperinflammatory” phenotype presenting with fever, arthritis and serositis, deserving similar aggressive therapeutic strategies as renal flares and burdened by a comparable proportion of unsatisfying response to treatment.

PV244 / #178Poster Topic:AS24 - SLE-TreatmentBackground/PurposeRisk for infections in systemic lupus may arise from immunosuppressant treatments or intrinsic immune defects. Disordered interferon signals are a hallmark of SLE. Anifrolumab, which targets the Type I Interferon Receptor (IFNAR), has been found to be safe and effective but, not surprisingly, inhibition of interferon signals is associated with some viral infections and herpes zoster reactivation. We previously reported a relationship between interferon activation and suppressed response to influenza vaccine.[1] The current study examined hemagglutinin inhibition and anti-influenza vaccine antibodies after the administration of flu vaccine in SLE patients on anifrolumab.MethodsBetween 2020 and 2023, 18 patients with active, moderate to severe SLE received 3 monthly doses of open-label anifrolumab 300 mg IV. Two weeks after dose 1, an FDA-approved quadrivalent, season-specific influenza vaccination was given, In the third season (2022-23), 6 additional SLE patients participated in the protocol without receiving anifrolumab. All patients continued standard-of-care treatment (SOC) (Figure 1). Vaccine response was quantified with a hemagglutinin inhibition assay (HAI) using predominate antigen of active strains each year, and results of an enzyme-linked immunosorbent assay (ELISA) measuring IgG to the relevant seasonal vaccine antigens. Comparison of responses before and after vaccination and in patients who did or did not receive anifrolumab was performed by non-parametric testing. The proportion in each group developing a 2-fold increase in values for each test at week 8 compared to baseline, utilized Fisher’s Exact Test. Confidence intervals were derived with the Exact Clopper-Pearson Method.Figure 1.Study DesignResultsIn a combined analysis merging data from all 3 years, anifrolumab treated patients had no observable deficits in vaccine response by either HAI (Figure 2A) or by antibody levels to the vaccine (Figure 2B). At week 8, geometric mean titers (GMTs) and geometric standard deviations (GSDs) for HAI were anifrolumab: 123.0 (5.39) and control: 69.6 (1.79). GMTs (GSDs) for anti-vaccine antibody concentrations were anifrolumab: 171.8 (3.59) μg/mL and control: 151.7 (2.62). Geometric mean fold rises (GMFRs) (GSDs) of HAI titers from baseline to week 8 were anifrolumab 1.6 (4.52), control: 3.0 (1.46) and GMFRs of anti-influenza IgG were anifrolumab: 1.5 (2.91) and control: 2.8 (3.61). No differences were noted when vaccine responses were evaluated separately for each influenza season. All 6 patients in the control group and 15 (78.9%) of patients in the anifrolumab group developed at least 1 adverse event (AE) during the study. All AEs were mild or moderate in intensity. There were no serious adverse events, deaths, adverse events of special interest, or adverse events leading to discontinuation of treatment. As an additional analysis, the SLEDAI Flare Index (SFI) was evaluated. There were 8 (42%) individual patients in the anifrolumab group and 6 (100%) of patients in the control group who were noted to have a flare, (p=0.0196). All flares were mild/moderate and either mucocutaneous or musculoskeletal. There were 8 total flares in the treatment group (n=19) and 11 (n=6) in the control group.Figure 2.A) Anifrolumab Impact on Hemagglutination Inhibition (HAI) after Influenza Vaccine B) Anifrolumab Impact on Anti-Influenza Virus IgG Concentrations after Influenza VaccineConclusionsHumoral antibody responses induced by seasonal influenza virus vaccination in adult SLE patients were comparable between patients receiving anifrolumab and those only receiving standard of care, with no evidence to suggest inhibition of vaccine response by anifrolumab. Anifrolumab was well tolerated with no unexpected safety findings in the context of influenza vaccination.

PV027 / #769Poster Topic:AS04 - BiomarkersBackground/PurposeSystemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by a highly variable disease course, including unpredictable flares that can lead to significant morbidity. Early identification of impending flares could improve patient management and outcomes. This study investigates whether measuring dynamic levels of autoantibodies can predict the occurrence of SLE flares.MethodsA cohort of 100 SLE patients was prospectively followed for 2 years, with visits scheduled every 3 months at the outpatient clinic of the University Medical Center, Utrecht, the Netherlands. At each visit, clinical parameters were recorded, including the presence or absence of a flare, assessed with the SELENA-SLEDAI Flare Index. Additionally, blood samples were collected, and blood biomarker levels, including antibodies associated with SLE as well as calprotectin as a marker of neutrophil activation, were semiquantitatively measured using the EliATMtechnology (Phadia AB, Sweden) on citrate plasma. To assess whether changes in these autoantibodies predicted the occurrence of a flare 3 months later, binary logistic regression analysis was performed. For patients who experienced a flare during follow-up, changes (Δ) in biomarker levels were calculated between baseline and the preflare timepoint. For patients without flares, the highest Δ value observed between any 2 time points was used (Figure).Figure.For no-flare patients, change in autoantibody values was calculated between all consecutive visits and the maximum Δ (ie, the maximum background dynamics in patients with stable disease) used. For flare patients, Δ between baseline and the visit prior to flare was calculated to assess dynamics preflare. aB2: anti-beta-2-glycoprotein-1; aCL: anti-cardiolipin. p&lt;0.05 statistically significant.ResultsThe cohort consisted of 100 SLE patients with a median age of 50 years (IQR 39-57); 88 women and 12 men. Regarding ethnic distribution, 77 patients were White, 9 Asian, and 4 Black. Median disease duration was 18 years (IQR 8-28). Median SLEDAI score at baseline was 4 (IQR 2-6). During follow-up, 132 flares were registered, of which 119 moderate and 13 severe. In the binary logistic regression analysis changes in La/SSB (OR 1.48, 95% CI 1.026-2.129), Ro52 (OR 1.03, 95% CI 1.004-1.047), and Ro60 (OR 1.04, 95% CI 1.007-1.076) were identified as significant predictors of a flare occurring within the following 3 months. RA33 IgA was inversely associated with flare risk (OR 0.20, 95% CI 0.053-0.757) (Table 1).Table 1:Results of binary logistic regression analysis assessing whether changes in autoantibody titers predict the occurrence of flares 3 months later.ConclusionsThese findings suggest that the dynamics over time of specific autoantibody levels, particularly La/SSB, Ro52, and Ro60, can serve as predictors for impending disease flares in SLE patients. Additionally, the inverse association of RA33 IgA with flare risk indicates a potential modulatory role in disease activity. Further research is needed to elucidate the underlying mechanisms of this findings and explore their clinical applicability in personalized disease management.

PV268 / #674Poster Topic:AS24 - SLE-TreatmentBackground/PurposeAnifrolumab (AFM) has demonstrated efficacy and safety in patients with systemic lupus erythematosus (SLE), but the effect of type I interferon modulation on the immune abnormalities in these patients is unclear. This study aimed to investigate the relationship between changes in immune phenotype and the efficacy of AFM in patients with SLE who experienced minor flares after lupus low disease activity state (LLDAS).MethodsPatients with SLE who achieved LLDAS but experienced minor flares due to mild or moderate organ damage according to the clinical items of the revised SELENA flare index were divided into 2 groups: Those who received standard of care (SoC, n = 18) with increased glucocorticoid (GC) doses or additional immunosuppressants and those who received only additional AFM treatment (n = 50). Effectiveness and safety were compared 26 weeks after intensification using propensity score-based inverse probability of treatment weighting (PS-IPTW). Peripheral blood immunophenotypes at baseline were analyzed and compared with age- and sex-matched healthy controls (HC, n=70) about the standardized NIH/FOCIS Human Immunophenotyping Consortium protocol. Immunophenotype changes and their impact on re-achieving LLDAS at Week 26 were also analyzed in SLE patients who experienced minor flares after LLDAS.ResultsAfter PS-IPTW adjustment, there were no differences in baseline characteristics between the groups. The 26-week persistence rate of the AFM group was 90.0% (45/50). The LLDAS achievement rate was significantly higher in the AFM group (SoC group: AFM group = 33%:87%, p &lt; 0.001). The SELENA-SLEDAI scores significantly decreased in both groups, and no significant difference was observed between the groups at 26 weeks (SoC group: AFM group = 2.1±2.0:1.8±1.7, p = 0.453). The mean dose of GC was markedly reduced in the AFM group (3.6±3.1→2.1±2.7, p &lt; 0.001), and the GC mean dose at Week 26 was significantly lower in the AFM group (SoC group: AFM group = 5.7±1.8:2.1±2.7, p &lt; 0.001), leading to GC discontinuation in 3 patients. The incidence of adverse events was significantly lower in the AFM group (SoC group: AFM group = 47%:12%, p &lt; 0.001), particularly for infections (SoC group: AFM group = 38%:12%, p &lt; 0.001). In peripheral blood immunophenotype analysis, in comparison with HC, SLE patients had a higher proportion of activated Tfh cells (p=0.003), activated Th17 cells (p=0.0025), and plasmocytes (p=0.015), and a lower proportion of naïve B cells (p=0.010). There were no significant differences in baseline immunophenotypes between the AFM and SoC groups. At 26 weeks, both groups exhibited decreased plasmocyte proportions. In the AFM group, the proportions of activated Th17 cells (p = 0.014), Tfh cells (p &lt; 0.001), and activated Tfh cells (p = 0.018) significantly decreased at 26 weeks compared to baseline. In both the SoC group and the AFM group, no baseline clinical features were associated with achieving LLDAS or DORIS remission. However, in the AFM group, patients with a higher baseline proportion of plasmocytes were more likely to achieve DORIS remission. In the SoC group, there were no peripheral blood immune phenotype characteristics associated with LLDAS or DORIS remission.ConclusionsIn SLE patients who experience a minor flare after achieving LLDAS, disease activity may be effectively controlled by adding AFM alone, without the need to increase immunosuppressants or glucocorticoids. Among these patients, AFM appears to be particularly effective in those with a high baseline proportion of plasmocytes prior to its initiation.

O063 / #228Topic:AS21 - Pregnancy and Reproductive HealthABSTRACT CONCURRENT SESSION 11: PREGNANCY IN SLE24-05-2025 10:40 AM - 11:40 AMBackground/PurposeFertility treatments, which involve the use of exogenous sex hormones, raise concerns about their safety in women with systemic lupus erythematosus (SLE).MethodsThis study included all pregnancies in women with SLE enrolled in the multicenter French prospective GR2 (Groupe de Recherche sur la Grossesse et les Maladies Rares, Clinicaltrial:NCT02450396) study, conceived before 1st August 2022, with available end-of-pregnancy data and known conception type.[1] Pregnancies were classified into 2 groups: those conceived naturally and those with assisted conception. Adverse pregnancy outcomes (APOs) were defined as the occurrence of an intrauterine fetal death after 12 weeks of gestation (WG), a placental insufficiency leading to preterm delivery before 37 WG, a small for gestational age, and/or a neonatal death.[1,2] Maternal flares were defined according to the SELENA-SLEDAI Flare Index. The main endpoint was the birth of a living child. Logistic regression was performed to assess whether fertility treatments were independently associated with live birth. Cumulative incidences of disease flares and APOs were also compared using Kaplan-Meier analysis (Cox regression model adjustment).Results630 pregnancies met eligibility criteria, including 577 pregnancies obtained naturally in 478 women and 53 pregnancies through assisted conception (2 ovulation inductions, 12 intrauterine inseminations, and 39 in vitro fertilizations (IVF)) in 48 women. The mean age of women was older (35.8 vs. 32.3 years,p&lt; 1.10^-4), and twins were more frequent in assisted pregnancies (5/50, 10.0% vs. 20/554, 3.6%;p= 0.047). Lupus disease was clinically inactive at baseline in 51/53 (96.2%) assisted pregnancies (vs 511/570, 89.6%;p= 0.15), with 10 of 45 (22.2%) having chronic damage (vs 65/513, 12.7%;p= 0.07). Lupus anticoagulant (LA) was present in 4/52 (7.7%) assisted pregnancies (vs 72/572, 12.6%;p= 0.38). Hydroxychloroquine was prescribed in 52/53 (98.1%) assisted pregnancies (vs 561/577, 97.2%;p= 1.0). About half of assisted and natural pregnancies (25/48, 52.1% vs 272/522, 52.1%;p= 1.0) were exposed to corticosteroids, but the daily prednisone dosage at inclusion was significantly higher in assisted pregnancies (median dose of 9 [IQR 5.0-10.0] vs. 5 [IQR 5.0-10.0] mg/day;p= 0.025). The live birth rate was similar between assisted and spontaneous pregnancies (46/53, 86.8% vs 505/577, 87.5%;p= 0.83). Assisted conception was not independently associated with achieving a live birth after adjusting for age, number of fetuses, gravidity, disease activity, damage, positive LA, exposure to low-dose aspirin, and daily prednisone dosage at inclusion (adjusted OR = 1.41 (95% CI 0.44-4.47),p= 0.56). At least one flare occurred in 9/53 (17.0%) assisted pregnancies (vs 96/565, 17.0%;p= 0.74). Among pregnancies progressing beyond 12 WG, at least one APO was reported in 8/48 (16.7%) assisted pregnancies (vs 86/525, 16.4%;p= 0.98). Cumulative incidences of flares, and APOs did not differ significantly between both groups. Fertility treatments did not appear to be an independent predictor of the occurrence of flare or APO after adjustment for confounding factors. When the analyses were limited to the group of pregnancies achieved by IVF, results remained unchanged.ConclusionsFertility treatments in women with mostly well-controlled SLE did not appear to increase risks of maternal and neonatal complications, supporting current recommendations.[3]

PV153 / #118Poster Topic:AS17 - MiscellaneousBackground/PurposeSystemic lupus erythematosus remains a disease of high unmet medical need. Protean manifestations and the lack of clear understanding of etiology, pathogenesis, and disease subgroups hinder the development and application of targeted therapeutic approaches. Community-wide access to a longitudinal, highly curated, centralized patient dataset with linked biospecimens and molecular data is critical to enable advances in this area. To address this unmet need, the Lupus Research Alliance created the Lupus Nexus (LNx), a lupus registry, biorepository and data exchange platform.MethodsTo ensure that the design of LNx reflected the needs of the research and patient communities, LNx was developed with guidance from over 100 individuals representing clinicians and scientists from academia and industry, governmental and nonprofit groups, and patients with lupus. A Steering Committee was formed to provide leadership, oversight and direction to the design, implementation and governance of LNx including the oversight of 8 Working Groups (WGs) (Table 1) charged with developing individual components of the program. Members of the WG included experts in clinician- and patient-reported outcomes, registries, biorepositories, bioinformatics, biospecimen analyses, and lived lupus experience. Many of these individuals have transitioned to roles on active Advisory Boards to continue to provide guidance on LNx operations. The LNx has 3 main components: a registry, a biorepository, and a data exchange platform. The registry and biorepository are first being established through the Lupus Landmark Study (LLS), a prospective, longitudinal observational study that began in 2023. The LLS will enroll up to 3,500 people living with lupus into 4 cohorts-new onset, extra-renal flare, active lupus nephritis, prevalent- and will follow them over 5 years. Participants are recruited from 24 sites across the LRA Lupus Clinical Investigators Network. The registry includes medical information (full medical, familial autoimmune, serological, medications, vaccination history), clinician-reported outcomes (SLEDAI Flare Index, SLICC/ACR Damage Index, neuropsychiatric SLE, SLEDAI-2K, PGA-VAS), and patient-reported outcomes (sociodemographic, health habits, SLAQ, PROMIS, Lupus Erythematosus Quality of Life). The biorepository includes genomic DNA, RNA, plasma, serum, PBMC[AK1], urine, saliva, stool and tissue. The data exchange platform is a federated Trusted Research Environment (TRE) that aggregates datasets and provides a high-performance infrastructure with portals for researcher and patient communities. The researcher portal allows for biospecimen search and data mining using native analytical tools, while the patient community portal allows individuals to view their study data with supportive interpretative services and to connect with other patients. Raw data from biospecimen analyses will be deposited in the TRE, amassing a deep and comprehensive dataset over time.Table 1.Steering Committee and Working Group overviewResultsAs of 11/04/24, there are 174 participants enrolled into the registry (Table 2). Actual enrollment in the 4 cohorts is 10% new onset, 18% active lupus nephritis, 25% extra-renal flare, and 46% prevalent cases, with 35% Black patients, 20% Hispanic/Latino patients, and 12% Asian/Pacific Islander patients. Over 2200 unique samples (subject x timepoint x sample type) have been collected and plans are underway for specific biomarker analyses to stimulate broader community utilization.Table 2.Recruitment demographicsConclusionsLNx is a unique resource for researchers and patients that will help accelerate precision medicine for lupus (www.lupusnexus.org). The LRA acknowledges the many experts that have contributed to its creation, especially those individuals living with lupus and their care partners.

To compare measurements of canal flare index (CFI) and greater trochanter overhang (TrO) from ventrodorsal (VD) and craniocaudal horizontal beam (CCHB) radiographic views to measurements from contemporaneously acquired CT scans and to evaluate the impact of size, age, radiographic view, severity of osteoarthritis, hip subluxation, and femoral rotational malposition on CFI and TrO measurement accuracy. This was a retrospective study of femurs imaged from June 28, 2018, through March 27, 2023. The CFI and linear TrO index measured from VD and CCHB radiographs and from CT-derived surface renderings of the femur prepared with -10°, -5°, 0°, +5°, and +10° of rotation using computer-aided design software were compared. 80 femora from 43 dogs were included. Radiographs measured CFI with errors > 0.2 in 81% of VD views and 77% of CCHB views and yielded linear TrO measurements with errors > 20% of canal radius in 75% of VD and 74% of CCHB views. The TrO grade was incorrect for 44% of femurs on VD views and 30% of femurs on CCHB views. Internal femoral rotation of 10° significantly influenced CT measurements of CFI and TrO. Severity of osteoarthritis and hip subluxation did not influence measurements. Measurements of CFI and TrO from VD and CCHB views are inaccurate relative to CT measurements. Radiographic measurements underestimate CFI and poorly predict TrO. A CT of the femur should be considered when accurate measurements of CFI and TrO are sought, particularly for femurs with abnormal geometry.

Abstract Solar flares, the significant indicators of solar activity, have an impact on Earth's satellites and communication systems. Accurate prediction of solar flare events is crucial for mitigating these effects. In this work, we use multiple data sources, including Geostationary Operational Environmental Satellites soft X‐ray flare flux and the solar flare index, to forecast solar flare activity during Solar Cycle 25 (SC25). Our results show that: (a) The north‐south asymmetry of solar flare activity during SC25 is well revealed, and the southern hemisphere is greater than the northern one. (b) The Gnevyshev peaks of chromospheric flare activity are clearly identified and they are deeper than other atmospheric activity indicators. The different timescales of solar flare responses to the geomagnetic and interplanetary magnetic fields may be the cause of the Gnevyshev peaks. (c) Chromospheric flare activity lags behind photospheric sunspot activity, indicating that changes in sunspot activity precede flare events. (d) The activity level of SC25 is influenced by the modulating effect of the Gleissberg Cycle, as supported by geomagnetic precursor indices. These results offer valuable insights into the temporal and spatial distribution of solar flare activity during SC25.