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Bilateral sacrospinous ligament fixation (BSSLF) is a well-established procedure for apical prolapse repair, yet surgical approaches and outcomes vary. This study presents the first large-cohort, long-term retrospective evaluation of BSSLF using the sling-like mesh Splentis®. We analyse anterior BSSLF (ABSSLF) outcomes without total hysterectomy and compare them with other surgical approaches used in clinical practice. A total of 391 patients treated with Splentis between 2012 and 2023 at two referral centres were stratified into group A (ABSSLF without total hysterectomy, n = 248) and group B (other approaches including posterior fixation and/or total hysterectomy, n = 143). Outcomes were evaluated at intermediate (1–3 years, n = 256) and long-term follow-up (> 3 years, n = 135). Primary endpoint was composite cure: Pelvic Organ Prolapse Quantification (POP-Q) point C < 0, absence of bulge symptoms and no retreatment. Secondary endpoints included POP-Q changes, patient-reported symptoms and complications. Overall cure was 90.3
BACKGROUND:Overactivation of the alternative complement pathway contributes to IgA nephropathy and glomerular inflammation. In the 9-month interim analysis of this phase 3 trial, iptacopan, a complement factor B inhibitor, led to a significant reduction of 38.3% in the 24-hour urinary protein-to-creatinine ratio as compared with placebo and had an acceptable safety profile. METHODS:In this phase 3 trial, we enrolled adults who had IgA nephropathy, an estimated glomerular filtration rate (eGFR) of at least 30 ml per minute per 1.73 m2 of body-surface area, and a 24-hour urinary protein-to-creatinine ratio of 1 or higher (with protein and creatinine both measured in grams) despite supportive care. Patients were randomly assigned, in a 1:1 ratio, to receive oral iptacopan (200 mg) or placebo twice daily. The primary end point for the final analysis was the annualized total eGFR slope as estimated over a 24-month period. Secondary end points included a composite kidney-failure end point (i.e., a sustained decline in eGFR of ≥30%, a sustained eGFR of <15 ml per minute per 1.73 m2, the initiation of maintenance dialysis, receipt of kidney transplant, or death from kidney failure), assessed in a time-to-event analysis. Safety was also assessed. RESULTS:Among 477 patients included in the final analysis, 238 had been randomly assigned to iptacopan and 239 to placebo. The annualized total eGFR slope was -3.10 ml per minute per 1.73 m2 per year with iptacopan, as compared with -6.12 ml per minute per 1.73 m2 per year with placebo (difference, 3.02 ml per minute per 1.73 m2 per year; 95% confidence interval [CI], 2.02 to 4.01; adjusted P<0.001). A composite kidney-failure end-point event occurred in 21.4% of the patients in the iptacopan group, as compared with 33.5% of those in the placebo group (hazard ratio, 0.57; 95% CI, 0.40 to 0.81; adjusted P = 0.003). The incidence of adverse events was 87.0% in the iptacopan group and 89.1% in the placebo group. Serious adverse events occurred in 12.2% of the patients who received iptacopan and in 11.7% of those who received placebo, and serious infections in 6.7% and 2.1%, respectively. No deaths occurred. CONCLUSIONS:Iptacopan therapy led to a significantly slower decline in kidney function than placebo. (Funded by Novartis; APPLAUSE-IgAN ClinicalTrials.gov number, NCT04578834.).
BACKGROUND:Latin America faces a high dementia burden, with increased prevalence of factors associated with cognitive decline. Multidomain lifestyle interventions might delay cognitive decline, but populations from Latin America remain under-represented in dementia prevention trials. We aimed to investigate the feasibility of a culturally adapted, multidomain, systematic lifestyle intervention and investigate its effects on global cognitive function in at-risk older adults (aged 60-77 years). METHODS:The LatAm-FINGERS Initiative for Cognitive Change (hereafter referred to as LatAm-FINGERS) was a single-blind, multicentre, randomised clinical trial conducted in 11 Latin American countries (Argentina, Bolivia, Brazil, Chile, Colombia, Costa Rica, Dominican Republic, Ecuador, Mexico, Peru, and Uruguay). Individuals aged 60-77 years with high risk of dementia (cardiovascular risk factors, ageing, and dementia risk score ≥6), and suboptimal cognitive performance were randomly assigned (1:1) to receive either a 2-year systematic lifestyle intervention (SLI group) or a flexible lifestyle intervention (FLI group). Randomisation was stratified by the study centre to ensure balance and implemented using permuted blocks of eight. Participants and intervention staff were not masked to group assignment, but individuals who assessed outcomes were masked throughout the trial. The SLI provided structured multidomain lifestyle interventions with supervised support and monitoring; FLI offered health advice. Primary outcomes were trial feasibility (evaluated using selected RE-AIM measures: Reach, Implementation, and Maintenance) and the intervention's effects on global cognitive composite trajectories over 2 years (change in the global cognitive composite score over 2 years). This trial is registered at ClinicalTrials.gov (NCT06492967) and has been completed. FINDINGS:Participants were enrolled between Oct 27, 2021, and July 7, 2023; the last participant completed follow-up on Nov 7, 2025. Among 1719 assessed, 1065 participants included in the analytic sample were randomly assigned to the SLI group (n=539) or the FLI group (n=526). Mean age was 67·5 years (SD 4·7), 795 (75%) of 1065 participants were women, and 270 (25%) were men. Self-reported race and ethnicity were: 624 (59%) Mestizo, 288 (27%) White, 72 (7%) Mulatto, 25 (2%) Mixed or other, 18 (2%) Black, 14 (1%) Indigenous, and 24 (2%) did not report race or ethnicity. 877 (82·3%) of 1065 completed the 2-year follow-up. Recruitment effectiveness (Reach) was 62·0%; mean adherence to the SLI group (Implementation) was 71·6% over the entire trial; and frequencies of complete cognitive outcomes data (Maintenance) were 87·9% at 6 months, 85·3% at 12 months, 81·4% at 18 months, and 84·8% at 24 months in the SLI group compared with 86·3% at 6 months, 78·9% at 12 months, 73·4% at 18 months, and 79·8% at 24 months in the FLI group. Dropouts were higher in the FLI group than in the SLI group (20·2% vs 15·2%; p=0·042). Global cognitive composite scores increased over time in both groups, with a mean annual change of 0·31 SD (95% CI 0·28-0·34) per year in the SLI group and 0·20 SD (0·17-0·23) per year in the FLI group (mean between-group difference of 0·11 SD per year [0·06-0·15; p<0·0001]). Overall, 478 adverse events were reported (412 in the SLI group and 66 in the FLI group). The most common adverse events were musculoskeletal symptoms (113 [21%] in the SLI group, 13 [2%] in the FLI group), upper respiratory infections (50 [9%] in the SLI group, one [<1%] in the FLI group), and COVID-19 infection (31 [6%] events in the SLI group). Serious adverse events occurred in 50 (9%) participants in the SLI group and 24 (5%) participants in the FLI group; none were related to the intervention. There were eight deaths (three in the SLI group and five in the FLI group), and none were related to the intervention. INTERPRETATION:A culturally adapted multidomain lifestyle intervention was feasible across Latin America and resulted in greater cognitive improvements than a flexible health-advice intervention in older adults at risk of cognitive decline. These findings extend the evidence base for multidomain lifestyle interventions to populations historically under-represented in dementia research, supporting their feasibility and scalability as strategies to reduce cognitive decline risk amid the rapidly growing burden of dementia in low-income and middle-income countries. FUNDING:Alzheimer's Association. TRANSLATIONS:For the Spanish and Portuguese translations of the abstract see Supplementary Materials section.
Patient-ventilator asynchrony is highly prevalent during invasive mechanical ventilation, yet its detection at the bedside remains limited. Conventional waveform inspection is intermittent, operator-dependent, and insufficient to capture the complexity and temporal variability of patient-ventilator interaction. Automated systems based on advanced signal processing and artificial intelligence represent a paradigm shift, enabling continuous, objective, and scalable detection of asynchrony. Recent approaches highlight the value of entropy-based metrics to quantify the irregularity of ventilatory signals and capture subtle changes in respiratory variability. Similarly, the identification of asynchrony clusters, periods where multiple asynchronous events occur in succession, provides a clinically relevant framework to stratify severity and predict outcomes. These developments underscore the superiority of automated methods over human observation alone. From an implementation perspective, centralized monitoring architectures offer greater potential than stand-alone devices, as they allow multimodal integration, data aggregation, algorithm refinement, and interoperability across platforms. Looking forward, research must expand toward the fusion of ventilatory, hemodynamic, and neurological signals to provide a comprehensive picture of patient-ventilator interaction. Particular attention should be paid to the long-term consequences of poor synchrony, as evidence suggests that asynchronies may influence functional recovery and health-related quality of life well beyond intensive care unit discharge. Robust, standardized datasets will ultimately support the generation of synthetic data and patient-specific digital twins, paving the way for precision-guided, adaptive mechanical ventilation.
Background: Sublingual immunotherapy (SLIT) is a well-established form of allergen immunotherapy with demonstrated efficacy and a favorable safety profile in IgE-mediated allergic diseases, particularly in allergic rhinitis and allergic asthma. Since the publication of previous World Allergy Organization (WAO) position papers, accumulating evidence and expanding global clinical experience has justified an updated, internationally harmonized framework to guide the appropriate use of SLIT across diverse healthcare settings. Methods: An international panel of experts developed an updated Position Paper on SLIT using a structured Delphi consensus methodology. Statements were formulated based on a targeted review of the scientific literature and expert clinical experience, addressing indications, patient selection, safety, treatment duration, adherence, biomarkers, disease modification, and implementation domains. Two rounds of anonymous electronic voting were conducted. Consensus was predefined as ≥70% agreement (scores 4–5 on a 5-point Likert scale). Results: Eighty-three experts representing all WAO regions were invited, and seventy-eight of them participated in the Delphi process. High levels of consensus were achieved for core principles, including SLIT effectiveness, safety, the importance of appropriate patient selection, a minimum treatment duration of 3 years, supervised administration of the first dose followed by home-based treatment, and the central role of adherence and regular follow-up. Consensus regarding disease-modifying effects was stronger for children and adolescents than for adults. Lower consensus was observed on topics related to regional allergens, likely influenced by differences in allergen exposure, product availability, clinical experience, and regulatory contexts; however, formal region-stratified analyses were not performed. Conclusions: This WAO Position Paper establishes a globally applicable, evidence-informed consensus framework for the positioning and implementation of SLIT. By clearly delineating areas of strong agreement and domains of conditional or context-dependent evidence, it provides both a clinical reference and a strategic roadmap for equitable and sustainable SLIT integration worldwide.
