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Background/importance Spinal cord stimulation (SCS) is an established therapy for chronic pain conditions when conventional treatments fail. However, global research implementation varies significantly due to patient demographics, healthcare infrastructure, and economic factors, creating disparities in access that directly impact patient care and public health outcomes. Objective To evaluate the global landscape of SCS research by analyzing patient demographics, geographic distribution, funding sources, and pain conditions treated across chronic pain populations aged 18 years and older, with primary focus on associations between geographic regions and patient age demographics. Evidence review We conducted a systematic literature review and meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, searching five major databases through October 2024. Studies from 2000 onward reporting SCS in adults with chronic pain lasting 3 months or longer were included. We included randomized trials, comparative studies, and case series with at least 10 patients, excluding commentaries, reviews, and insurance databases. Findings Analysis of 187 studies revealed heterogeneity in age distributions across geographic regions, with Asian studies showing higher mean ages compared to North America, while European showed lower mean ages. Research concentration was predominantly in high-income regions, with 57% of studies receiving industry funding and significant associations between funding source and geographic origin. Post-surgical pain syndrome-thoracolumbar emerged as the most prevalent condition globally, representing 44.9% of cases. Conclusions Significant associations exist between geographic regions and patient demographics in SCS research, with notable disparities in research concentration highlighting the need for broader investigation in underrepresented areas to optimize global application of this chronic pain management therapy. PROSPERO registration number CRD42025635147.

ObjectiveIn the phase 3 head‐to‐head MANDARA study (NCT04157348), benralizumab demonstrated noninferiority to mepolizumab in inducing remission (defined as Birmingham Vasculitis Activity Score [BVAS] of 0 and oral glucocorticoid [OGC] dosage ≤4 mg/day at weeks 36 and 48) in patients with eosinophilic granulomatosis with polyangiitis (EGPA). This analysis investigated a more stringent definition of remission that included discontinuation of OGCs and being relapse‐free.MethodsPatients aged ≥18 years with documented relapsing or refractory EGPA receiving OGCs at ≥7.5 mg/day with or without immunosuppressive therapy for ≥4 weeks before enrollment were randomized (1:1) to benralizumab at 30 mg or mepolizumab at 300 mg subcutaneously every 4 weeks for 52 weeks. The proportion of patients achieving remission off OGCs, defined as BVAS of 0, OGC dose of 0 mg/day (at weeks 36 and 48) and no relapses during the double‐masked period, was assessed.ResultsPatients (n = 140) were randomized to benralizumab (n = 70) or mepolizumab (n = 70). The adjusted percentage of patients with remission off OGCs was 23.5% (n = 16) with benralizumab versus 11.1% (n = 8) with mepolizumab (difference 12.47 [95% confidence interval 0.46–24.48], P = 0.042). Of those who achieved remission off OGCs, 100% of benralizumab‐treated patients and 98.6% of mepolizumab‐treated patients achieved remission within the first 36 weeks of treatment.ConclusionThe administration of anti–interleukin‐5/receptor (IL‐5/R) therapies, benralizumab and mepolizumab, enable discontinuation of OGCs in some patients with EGPA, while avoiding relapses. These findings suggest that adding anti‐IL‐5/R therapy to standard primary treatment for patients with EGPA may improve response.

Acute myeloid leukemia (AML) is an aggressive hematologic malignancy characterized by the clonal proliferation of myeloid precursors and rapid progression. Historically consisting of intensive chemotherapy, AML management has evolved significantly due to advances in molecular diagnostics and risk stratification. This review discusses current therapeutic paradigms in AML, emphasizing the growing role of personalized medicine across age and risk groups. For younger, fit patients, intensive regimens such as the “7 + 3” protocol remain the standard, often enhanced by targeted agents like FMS-like tyrosine kinase 3 (FLT3) and IDH inhibitors. Older or unfit individuals benefit from low-intensity treatments such as hypomethylating agents combined with venetoclax, now considered a frontline standard of care. The use of liposomal chemotherapy (CPX-351), measurable residual disease (MRD) monitoring, and maintenance therapy further refine post-remission strategies. Emerging therapies, including menin inhibitors, antibody–drug conjugates, and immunotherapies like CAR-T cells and vaccines, offer additional options, especially in relapsed/refractory settings. This comprehensive review outlines the current landscape and future directions in AML therapy, emphasizing the transition toward individualized, mutation-driven treatment strategies.

Abstract Despite significant therapeutic advances in multiple myeloma (MM), outcomes in patients with plasma cell leukemia (PCL) remain dismal. We conducted a multicenter retrospective analysis of patients with PCL who were treated with the B-cell maturation antigen–directed chimeric antigen receptor T-cell (CAR-T) products idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel). We identified 34 patients; 19 patients received ide-cel and 15 received cilta-cel. With a median follow-up of 11.9 months, the overall median progression-free survival (mPFS) was 9.0 months (95% confidence interval [CI], 4-15) and the median overall survival (mOS) was 13.0 months (95% CI, 8 to not estimable [NE]). The 1-year cumulative incidence of progression or death was 72%, and the 1-year cumulative incidence of death was 47%. Patients who received cilta-cel had a longer mPFS (19.0 months vs 6.0 months) and mOS (>23 months [NE] vs 9.0 months) when compared with those treated with ide-cel. Similarly, the 1-year cumulative incidence of disease progression or death was 37.5% (95% CI, 17.4-68.5) with cilta-cel, whereas all patients treated with ide-cel progressed or died within 12 months of infusion. The rates of hematologic and nonhematologic toxicities were similar between patients treated with cilta-cel and those treated with ide-cel and were consistent with those reported in patients with MM. In this first multicenter study that evaluated patients with PCL who were treated with standard-of-care CAR-T products, we show that CAR-T is safe, feasible, and associated with improved outcomes when compared with historic standards.

Introduction: Endovascular thrombectomy (EVT) is an effective treatment for basilar artery occlusion (BAO) stroke in select patients. While there is a growing body of literature suggesting that advanced imaging modalities such as computed tomography perfusion (CTP) and magnetic resonance (MR) may not be necessary for selecting anterior circulation large vessel occlusion stroke patients for EVT, whether advanced imaging may be superior to conventional imaging (non-contrast CT and CT angiography) in identifying good treatment candidates among BAO patients is less clear. Patients and methods: This was a multicenter retrospective cohort study of BAO EVT patients treated from 2013 to 2022 in the Stroke Thrombectomy and Aneurysm Registry. Patients selected for EVT by advanced imaging (CTP or MR) were matched with those selected by conventional imaging using propensity score matching (PSM) accounting for possible confounders. Primary outcome was functional independence at 90 days. Other outcomes include bedridden state or death at 90-days and symptomatic intracranial hemorrhage (sICH). Results: 268 patients were included. 150 patients were selected for BAO EVT by conventional imaging, 86 by CTP, and 32 by MR. Patients selected by advanced imaging were significantly older than those selected by conventional imaging (median age 71 vs 64 years, p = 0.001); patient characteristics were otherwise similar between cohorts. After PSM, 90-day outcomes were similar between the two cohorts ( p = 0.56), with similar rates of functional independence (39.4% vs 35.1%, p = 0.65), bedridden state or death (40.4% vs 44.7%, p = 0.66), and sICH (3.3% vs 5.7%, p = 0.49) for conventional and advanced imaging groups, respectively. Results were similar across treatment time windows (all p > 0.05). Conclusions: Selecting patients for basilar EVT using conventional versus advanced imaging did not result in different clinical outcomes, regardless of treatment time windows. Conventional imaging appears sufficient as a first-line tool for selecting basilar EVT patients in routine clinical practice.

Atrial natriuretic peptide (ANP) is suggested to stimulate lipolysis, which has been demonstrated using supraphysiological doses of ANP. We explored the effects of physiological doses of ANP, as observed during an acute exercise bout, on lipolysis, ketogenesis, and glucose metabolism. Ten healthy men was randomized to infusion of ANP vs. placebo using stable isotope labeled tracers. The present study indicates that lipid metabolism does not seem to be regulated by ANP in men.

Abstract Background Breast cancer genome-wide association studies (GWAS) have identified more than 200 susceptibility loci, but most studies are dominated by European and East Asian populations. Methods We analyzed breast cancer GWAS summary statistics from African (AFR), East Asian (EAS), European (EUR), and Hispanic/Latina (H/L) samples (159,297 cases and 212,102 controls). We estimated logit-scale SNP-based heritability, polygenicity, and cross-ancestry genetic correlation, partitioned heritability across functional annotations, and integrated GWAS results with the Tabula Sapiens single-cell atlas using scDRS+. Results The logit-scale heritability of breast cancer ranged from ℎ 2 =0.47 (SE = 0.07) in EAS to AFR ℎ 2 =0.61 (SE = 0.10), with no significant differences across ancestries (p=0.63). The estimated number of susceptibility markers in a sparse normal-mixture effects model also varied from 4,446 (SE = 3,100) in EAS to 8,308 (SE = 2,751) in AFR, but differences were not significant across ancestries (p=0.55). Cross-sample genetic correlations varied, with the strongest correlation between EUR and EAS (𝜌 = 0.79, SE = 0.08) and weakest between AFR and H/L (𝜌 = 0.26, SE = 0.24). Regulatory annotations were enriched for breast cancer heritability across samples. Integration with single-cell expression profiles implicated ancestry-shared associations with innate immune, secretory epithelial, and stromal cell types. Conclusion These results indicate substantial cross-ancestry sharing of breast cancer polygenic architecture, highlight a consistent contribution of regulatory variation, and identify convergent cellular contexts that motivate functional follow-up and inform expectations for the transferability and attainable performance of common-variant risk prediction across populations.

Abstract Rationale High-attenuation area (HAA) is a computed tomography (CT) tool that correlates with lung inflammation and fibrosis. Systemic molecular correlates of HAA (e.g., plasma proteins) may inform biological processes involved in interstitial lung disease. Objectives To identify plasma proteins that associate with HAA and correlate with a higher probability of developing new-onset fibrotic or subpleural interstitial lung abnormalities (ILAs). Methods Plasma protein levels were measured using a semiquantitative aptamer-based platform in MESA (the Multi-Ethnic Study of Atherosclerosis; N = 5,486) and SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study; N = 1,781). Linear regression models identified HAA-associated proteins after adjustment for demographic and socioeconomic factors, CT scanner parameters, study center, and batch. Associations of HAA-related proteins with new-onset fibrotic or subpleural ILAs were examined in MESA participants with ILA assessments on full-lung CT 10 years later. Immunohistochemical staining of select proteins was performed in lung tissue from pulmonary fibrosis cases. Measurements and Main Results There were 75 proteins detected that were significantly associated with HAA in MESA and SPIROMICS. Gene Ontology analysis of these proteins identified processes involved in immune cell chemotaxis and cellular growth and apoptosis. Seven proteins were associated with a higher probability of new-onset fibrotic or subpleural ILAs in MESA, and two of these, junctional adhesion molecule-like protein and GTP cyclohydrolase 1 feedback regulatory protein, stained in areas of fibrosis in lung tissue from patients with interstitial lung disease. Conclusions Plasma proteins associated with more HAA are involved in immune and cellular processes and associate with new-onset fibrotic-subpleural ILA.

Objectives: To describe changes in the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) exam in sublesional motor and sensory domains following short-term epidural electrical stimulation of lumbosacral spinal segments in individuals with spinal cord injury (SCI). Methods: Twenty individuals with SCI underwent implantation of percutaneous epidural spinal cord stimulation followed by stimulation parameter optimization and 10-12 sessions of stimulation-enabled motor training. Pre-/postintervention ISNCSCI exams were compared to determine changes in motor/sensory scores for regions within 3 levels of the neurological level of injury (NLI) and caudal to this, with subanalyses per motor/sensory complete versus incomplete baseline status. Results: Individuals with motor complete SCI gained 6% ± 3% of available motor points within 3 levels of NLI and 1% ± 0% of motor points caudal to this ( P = .08). Motor incomplete individuals gained 9% ± 22% of available motor points within 3 levels of NLI and lost 4% ± 7% of motor points caudal to this ( P = .63). Following stimulation, changes in motor scores with potential high functional impact occurred in 3 individuals (5 total muscle groups with conversion from baseline <3/5 strength to ≥3/5 at completion). Individuals with sensory complete SCI had fewer sensory gains within 3 levels of NLI (6%) compared to those with sensory incomplete SCI (30%, P = .02). Discussion: Spinal cord stimulation after SCI rapidly induces changes in both motor and sensory domains that are retained after stimulation is removed. These changes primarily occur within 3 levels of the NLI and occur to a greater degree in those with incomplete SCI.