Citations

Objective To provide evidence‐based and expert guidance for the treatment and management of non‐renal systemic lupus erythematosus (SLE); treatment and management of lupus nephritis are addressed in a separate guideline. Methods Clinical questions for treatment and management of SLE were developed in the PICO format (population, intervention, comparator, and outcome). Systematic literature reviews were developed for each PICO question, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology was used to assess evidence quality and formulate recommendations. The Voting Panel achieved a consensus of ≥70% agreement on the direction (for or against) and strength (strong or conditional) of each recommendation. Results We present recommendations and ungraded, consensus‐based good practice statements for the treatment and management of SLE that are applicable to pediatric and adult patients. Recommendations emphasize uniform treatment with hydroxychloroquine, limiting duration of glucocorticoid use, and early introduction of conventional and/or biologic immunosuppressive therapies to achieve and maintain control of SLE inflammation (remission or a low level of disease activity), reduce SLE‐related morbidity and mortality, and minimize medication‐related toxicities. Conclusion This guideline presents direction regarding treatment and management of SLE and provides a foundation for well‐informed, shared clinician–patient decision‐making. These recommendations should not be used to limit or deny access to therapies, as treatment decisions may vary due to the unique clinical situation and personal preferences of each person with SLE.

Background The Woven EndoBridge (WEB) device represents an innovative solution for cerebral aneurysm occlusion, particularly for challenging wide-neck bifurcation aneurysms. However, factors affecting sustained occlusion remain poorly understood. We utilized machine learning to attempt to identify predictors of favorable long-term outcomes following WEB treatment. Methods In this multicenter retrospective study, we collected patient demographics, aneurysm characteristics, procedural details, and clinical outcomes. The primary endpoint was improvement in occlusion status, defined as maintained Raymond-Roy Occlusion Classification (RROC) grade 1, or improvement from grade 2 to 1, or from grade 3 to either 2 or 1 on final angiographic follow up. The dataset was split into training (75%) and validation (25%) sets. The CatBoost algorithm was selected based on performance metrics, with Shapley Additive exPlanations (SHAP) values calculated to determine feature importance. Furthermore, a multivariable binomial logistic regression model was performed to validate machine learning findings. Results Among 720 aneurysms from 36 hospitals, 84% showed improvement in occlusion at follow up. Both machine learning and multivariable logistic regression identified aneurysm height as the most consistent correlate of nonimprovement (odds ratio (OR) 0.90 per mm, p = 0.022). In the CatBoost model, the highest-ranking features by SHAP included aneurysm height, patient age, treatment acuity, ACom location, WEB-SLS device, bifurcation anatomy, aneurysm multiplicity, baseline modified Rankin Scale, access route, and partial thrombosis. Conclusions Machine-learning and regression analyses identified consistent predictors of occlusion improvement after WEB treatment, with aneurysm height most strongly linked to nonimprovement. These insights may guide patient selection and follow up. Findings require cautious interpretation and external validation in larger cohorts.

Introduction: PH increases RV afterload, often leading to RV systolic and diastolic failure. The metabolic mechanisms underlying RV dysfunction remain poorly understood and are largely unexplored across non-PAH forms of PH. Aims: We aimed to identify which metabolites and metabolic pathways associated with imaging measures of RV systolic function. Methods: We analyzed data from the multi-center PVDOMICS cohort, which includes echo, CMR, invasive hemodynamics, clinical phenotyping, and untargeted plasma metabolomics (via Metabolon). RV systolic function metrics selected as the outcome measures for this study were fractional area change (echo), global longitudinal strain (echo), and RVEF (CMR). Associations between non-xenobiotic, named metabolites and RV function measures were assessed using linear regression adjusted for age, sex, BMI, and PH group, with significance defined by FDR <0.05. Metabolite set enrichment analysis (MSEA) was performed to identify significantly enriched pathways (FDR <0.20). To complement MSEA, we conducted mean-aggregation analysis: we averaged metabolite concentrations within each pathway and tested associations with RV function using the same covariate adjustments (FDR <0.05). Results: We identified 979 participants with plasma metabolomics and at least one available outcome measure (317 Group 1 PH; 106 Group 2 PH; 140 Group 3 PH; 51 Group 4 PH; 26 Group 5 PH; 81 Healthy Controls; 258 Disease Comparators). Linear regression identified 170 metabolites from the 647 named metabolites significantly associated with all 3 RV metrics (Top 10 by average ranked p-value displayed in Image 1 ). MSEA revealed seven enriched pathways across all RV metrics: Androgenic Steroids, Pregnenolone Steroids, Progestin Steroids, Fatty Acid Metabolism (Acyl Choline), Histidine metabolism, Vitamin A metabolism, Gamma-glutamyl Amino Acid ( Image 2) . Mean aggregation analysis showed that higher concentrations of Androgenic/Pregnenolone Steroids and Vitamin A metabolites strongly associated with improved RV function, while higher levels of Fatty Acid Metabolism (Acyl Carnitine) and Acetylated Peptides associated with worse function ( Image 3 ). Conclusions: Using data from the multi-institutional PVDOMICS cohort, we provide a blueprint of metabolites and metabolic pathways associated with RV systolic function across the spectrum of PH. Steroid hormones as well as Vitamin A and fatty acid metabolites emerged as central to RV systolic function.

Background Older adults undergoing percutaneous coronary intervention (PCI) face unique challenges due to complex anatomy and comorbidities. Intravascular imaging [including intravascular ultrasound (IVUS) and optical coherence tomography (OCT)] has been shown to improve PCI outcomes, but its benefits in older adults are less well established. We conducted a meta-analysis of randomized controlled trials (RCTs) to compare intravascular imaging with angiography alone to guide PCI in older adults. Methods Cochrane, PubMed, and Scopus were searched for RCTs comparing intravascular imaging (IVUS or OCT) vs. angiography alone in adults aged ≥65 years. The outcome of interest was major adverse cardiovascular events (MACE) at the longest follow-up, as defined by each trial. Subgroup analyses were performed based on intravascular imaging modality, age group, and lesion complexity. Data were pooled using random-effects models, and heterogeneity was assessed using Higgins’ I ² statistic. Results Nine RCTs ( n = 7164, intravascular imaging = 3703, angiography alone = 3461) met the inclusion criteria. Intravascular imaging significantly reduced MACE compared with angiography alone [relative risk (RR) 0.66, 95% confidence interval (CI) 0.56–0.77; P < 0.001; I ² = 0%]. IVUS demonstrated superiority over angiography alone (RR 0.55, 95% CI 0.43–0.72; P < 0.001; I ² = 0%), while OCT demonstrated only a trend toward MACE reduction (RR 0.80, 95% CI 0.62–1.02). Subgroup analyses indicated consistent benefits with intravascular imaging for adults aged ≥65 and ≥70 years, respectively, and among those with complex coronary lesions (RR 0.65, 95% CI 0.53–0.79; P < 0.001). Conclusion Intravascular imaging guidance, especially IVUS, reduces MACE in older adults undergoing PCI compared with angiography alone.

Purpose To compare clinical outcomes between augmented subchondral drilling (aSCD) and nonsubchondral drilling (NoSCD) techniques, both using a cartilage scaffold, in the treatment of isolated patellar cartilage lesions. Methods A retrospective cohort study was conducted on patients who underwent surgical treatment for isolated patellar cartilage using either an aSCD technique (a subchondral drilling augmented with a particulated cartilage allograft scaffold or a flexible osteochondral allograft scaffold) or a NoSCD technique (a particulated juvenile articular cartilage scaffold or a flexible osteochondral allograft scaffold implanted without performing a subchondral drilling). Patients were included if they had a minimum 2‐year follow‐up and excluded if they underwent concomitant meniscal or ligamentous procedures. While tibial tubercle osteotomy (TTO) was commonly performed, it was not a strict inclusion criterion. All procedures were performed through arthrotomy with a standardized postoperative rehabilitation protocol. Clinical outcomes included International Knee Documentation Committee (IKDC) and Lysholm scores, reoperation rates, conversion to total knee arthroplasty, and complications. Results A total of 65 knees were included: 31 in the aSCD group and 34 in the NoSCD group, with a mean follow‐up of 50.4 months (range, 24‐88 months). In the aSCD group, particulated allograft cartilage hydrated with platelet‐rich plasma was used in 80.7% of cases and flexible osteochondral allograft in 19.3%, while the NoSCD group was treated with Cartiform (Arthrex) in 70.6% and particulated juvenile articular cartilage in 29.4% of cases. TTO was performed in 87.0% of aSCD and 91.2% of NoSCD cases. Average defect sizes were 3.7 cm 2 (aSCD) and 4.0 cm 2 (NoSCD). At final follow‐up, the NoSCD group had significantly better outcomes, with higher median IKDC scores (81.0 vs 74.0; P < .001) and median Lysholm scores (83.0 vs 77.0; P < .001). A significantly greater proportion of NoSCD patients exceeded the minimal clinically important difference for IKDC (100% vs 80.6%; P = .024) but not for Lysholm (97.1% vs 93.5%; P = .935) at final follow‐up. In multivariable regression adjusting for scaffold type, TTO, and defect size, aSCD remained a significant independent predictor of lower final IKDC (β = –8.97; P = .001) and Lysholm (β = –12.71; P < .001) scores. The aSCD group had a significantly higher rate of repeat surgery (45.2% vs 14.7%; P = .015). There was no significant difference in conversion to total knee arthroplasty between groups ( P = .432). Conclusions For the treatment of isolated patellar cartilage lesions, a nonsubchondral drilling technique with scaffolding was associated with improved patient‐reported outcomes and fewer complications compared to a subchondral drilling technique with scaffolding, although there was no difference in the rate of conversion to total knee arthroplasty. Level of Evidence Level III, retrospective comparative study.

Abstract Purpose: AXL, a receptor tyrosine kinase related to oncogenic processes, is aberrantly expressed in various cancers and associated with treatment resistance. Enapotamab vedotin (EnaV), a novel anti-AXL human IgG1 and monomethyl auristatin E antibody–drug conjugate, demonstrated antitumor activity in preclinical models, including non–small cell lung cancer (NSCLC). This phase 1/2 study assessed the safety and preliminary efficacy of EnaV in solid tumors. Patients and Methods: This study comprised dose-escalation and dose-expansion phases; both phases investigated EnaV once every 3 weeks (Q3W) and EnaV on days 1, 8, and 15 of a 28-day cycle (3Q4W). Primary objectives determined the maximum tolerated dose (dose escalation) and safety (dose expansion). Pharmacokinetic profile, antitumor activity, and AXL expression were also assessed. Results: During dose escalation, 32 patients received EnaV Q3W; 15 received EnaV 3Q4W. The maximum tolerated dose and recommended phase 2 dose were 2.2 mg/kg in Q3W and 1.0 mg/kg in 3Q4W schedules. In dose expansion, 189 patients received EnaV Q3W; 70 received EnaV 3Q4W. Common adverse events in dose expansion included fatigue, constipation, nausea, decreased appetite, and diarrhea. Overall response rates ranged from 4.5% to 12.5% with Q3W dose schedule and from 9.1% to 11.5% with 3Q4W dose schedule. Disease control rates for NSCLC cohorts were 40.9% to 50.0%. NSCLC subset analysis demonstrated correlation between radiomics signature and disease control. The relationship between clinical activity and AXL expression was not apparent. Conclusions: EnaV had an acceptable safety profile; however, because the evaluation of antitumor activity did not show clinically meaningful responses, clinical development of EnaV was discontinued. Significance: EnaV, an anti-AXL human IgG1 and monomethyl auristatin E antibody–drug conjugate, showed single-agent antitumor activity in preclinical models. This phase 1/2 study of EnaV demonstrated a manageable safety profile and antitumor activity in selected tumor types. Further studies exploring alternative targeting modalities, patient selection, and/or combinations are needed.

Objective To determine the proportion of cases of lower extremity symptoms attributable to underlying musculoskeletal ( MSK ) rather than thrombotic etiologies in emergency versus non‐emergency settings. Methods We retrospectively reviewed all lower extremity Venous Doppler ultrasounds performed on emergency department ( ED ) and non‐ ED patients over a 1‐year period at a single institution. Using radiology report data mining software, keywords including tear, tendon, hematoma, and muscle were used to identify cases of MSK pathology of the lower leg. All reports were also reviewed for findings of venous thrombosis. Statistical significance between ED and non‐ ED patients for both incidental MSK pathology and venous thrombosis was assessed using chi‐squared tests. Results A total of 5714 lower extremity Doppler ultrasounds were performed at a single institution during the 1‐year period, 1829 in the ED and 3885 in non‐ ED settings. Sixty‐nine of 1829 (3.8%) ED patients had incidental MSK pathology of the lower extremity compared to 53/3885 (1.4%) in the non‐ ED setting ( p < .001). Two hundred sixty‐seven of 1829 (14.5%) ED patients had evidence of venous thrombosis and/or chronic post‐thrombotic change. When combined with thrombotic pathology as positive cases, incidental MSK injury accounted for 69/336 (20.5%) of ED cases with positive sonographic findings. Conclusions MSK pathology of the lower leg is significantly more likely to contribute to lower extremity symptoms in the ED compared to a non‐ ED setting. Therefore, a brief sonographic evaluation of the MSK apparatus may be beneficial in a subset of ED patients, particularly those with focal pain but no identifiable thrombotic etiology.