Objective To evaluate the efficacy, safety and predictive factors of belimumab (BEL)-based triple therapy in proliferative lupus nephritis (LN) in real-world settings.Methods We conducted a multicentre, retrospective study including patients with proliferative LN (new-onset or relapsing) who initiated BEL within 6 months of a renal flare, in combination with standard-of-care.Results 49 patients were included (mean age 37 years; 85.7% female; 67.3% Caucasian). The median time from renal flare to BEL initiation was 1 month (IQR 0–3). By 12 months, 67.3% achieved complete renal response (CRR), 75.5% primary efficacy renal response (PERR) and 83.7% at least partial renal response. Median proteinuria declined from 2.7 g/day to 0.49 g/day, with parallel improvement in estimated glomerular filtration rate (71 to 78 mL/min/1.73 m²). Patients with baseline proteinuria <3 g/day achieved significantly higher CRR (78.1% vs 47.1%; p=0.027) and PERR (84.4% vs 58.8%; p=0.048) rates.The mean glucocorticoid (GC) dose decreased from 31.7 mg/day at baseline to 3.5 mg/day at 12 months, and 26.1% of patients achieved complete GC withdrawal. Extrarenal disease activity was present in 81.6% of patients at baseline, predominantly articular and mucocutaneous, with clinically meaningful improvement in 80% during follow-up. At 12 months, 40.8% met remission by Definition Of Remission In Systemic Lupus Erythematosus (DORIS) criteria and 46.9% attained Lupus Low Disease Activity State (LLDAS). Renal treatment failure occurred in 16.3% and renal relapse in 4.1%. Adverse events were mild, and no serious BEL-related events were observed.Conclusion BEL-based triple therapy is effective and safe in proliferative LN, achieving high renal and extrarenal response rates, substantial GC-sparing and treat-to-target outcomes in real-world practice.
Predicting disease progression at the individual level is essential for personalized medicine. We previously developed machine-learning tools to estimate 5-year progression risk in people with multiple sclerosis (PwMS). Such models should account for disease-modifying therapy (DMT) and objective outcome definitions. In a retrospective multicenter case–control study, we evaluated adults with relapsing–remitting multiple sclerosis (RRMS) at baseline. Using machine-learning, we developed two complementary tools for individualized 5-year risk estimation: DAAE-M, optimized for transparency, software-neutral use, and mitigation of indication bias, and ELIE, optimized for dynamic landmark-based modeling, complex treatment histories, and mitigation of immortal-time bias. Disease progression was defined using both a clinical outcome (RRMS-to-progressive MS) and an objective outcome (late-stage confirmed progression independent of relapse activity). Among 34,510 people with RRMS (72.6
Background: Frailty has emerged as a critical factor to predict postoperative outcomes in elderly surgical patients. This study aimed to evaluate the prevalence of frailty and its association with morbidity and mortality after elective and emergency general surgery in older adults across Spain, using two validated screening tools: the Clinical Frailty Scale (CFS) and PRISMA-7. Methods: We conducted a prospective, multicenter observational study including 32 Spanish hospitals. Patients aged >70 years undergoing general surgery between October and December 2022 were consecutively enrolled. Frailty was assessed preoperatively using CFS and PRISMA-7. The primary endpoint was 30-day mortality; secondary outcomes included overall postoperative complications, severity of complications, and hospital readmissions. Surgical complexity was categorized using the Operative Severity Score. Predictive performance was assessed using ROC curves. Results: A total of 2051 patients were included (median age 77). Frailty prevalence was 39.5% using CFS and 40.8% according to PRISMA-7. Overall, 30-day mortality was 6.2%, and 34% experienced at least one postoperative complication. Both scales showed good predictive value for mortality (AUROC 0.77 for CFS and 0.75 for PRISMA-7) but limited capacity for predicting complications or hospital readmissions (AUROC < 0.65). Frailty was independently associated with increased mortality, especially in procedures of higher complexity. Conclusions: Frailty is highly prevalent in elderly surgical patients and is a strong predictor of 30-day mortality. The systematic screening of frailty using validated tools such as the CFS and PRISMA-7 should be incorporated into perioperative care pathways to enhance risk stratification and support clinical decision-making.
Mutations in FLT3 are present in approximately 30% of patients with AML. The addition of midostaurin (MIDO) to intensive chemotherapy (IC) became standard of care following the RATIFY trial, but comprehensive real-world data spanning the full adult age spectrum and including both FLT3-ITD and FLT3-TKD mutations remain limited. We retrospectively analyzed 1658 adults aged 14-85 years with newly diagnosed FLT3-mutated AML from 129 PETHEMA registry centers: 469 received IC + MIDO and 1189 IC alone. Composite complete remission was higher with IC + MIDO than IC (81.4% vs. 71.7%; p < 0.001) and Day 30 mortality was substantially lower (2.1% vs. 7.1%; p < 0.001). Median overall survival was 47.2 versus 19.3 months (HR 0.64; 95% CI, 0.53-0.76; p < 0.001), and the benefit was sustained after multivariable adjustment (HR 0.73; p = 0.017). In 261 propensity score-matched pairs, the effect was attenuated, remaining significant for event-free survival (HR 0.77; p = 0.029) and showing a nonsignificant trend for OS (HR 0.77; p = 0.06). Allogeneic hematopoietic stem cell transplantation in first remission was more frequent in the IC + MIDO cohort (48.9% vs. 41.3%; p = 0.023). Time-dependent analyses showed the largest MIDO effect among autologous and non-transplanted patients (OS HR 0.45; p = 0.138, and HR 0.69; p = 0.014, respectively). The benefit of MIDO was consistent irrespective of FLT3 mutation type, FLT3-ITD allelic burden, cytogenetic risk, and gender, while less improvement occurred among NPM1 wild type and secondary AML patients. This large real-world cohort confirms the survival benefit of MIDO plus IC across the full adult age spectrum, supporting its standard-of-care status in FLT3-mutated AML.
