Background: Highly effective CFTR modulator therapy has substantially changed the clinical course of cystic fibrosis (CF), but the magnitude of treatment response may vary according to baseline lung function. We evaluated the real-world effects of elexacaftor/tezacaftor/ivacaftor (ETI) in people with CF aged >6 years across a broad range of baseline lung function. Methods: In this observational study, 62 people with CF (23 male; age range 7.8–36.8 years) who were eligible for ETI according to genotype underwent assessment at treatment initiation and after 6 months. Assessments included spirometry, respiratory oscillometry, body composition and biochemical measurements. Results: Mean ppFEV1 increased from 94% at baseline to 108% after 6 months (p < 0.001), while mean FEF25–75 increased from 77% to 100% predicted (p < 0.001). Lower baseline ppFEV1 was associated with a greater ppFEV1 response (r = −0.596, p < 0.001), and baseline ppFEV1 remained the only significant factor associated with ppFEV1 change in multivariable analysis (β = −0.21, p = 0.006). Improvement was greater among participants with baseline ppFEV1 < 90%, although a measurable increase was also observed in those with ppFEV1 ≥ 90%. BMI increased significantly. HDL and LDL cholesterol increased (p = 0.007 and p = 0.011, respectively), whereas C-reactive protein decreased (p < 0.001). Changes in oscillometry were modest and provided limited additional information beyond spirometry in this cohort. Conclusions: ETI was associated with significant improvements in lung function in people with CF aged >6 years, including those with preserved baseline spirometry. The magnitude of ppFEV1 improvement was greatest in participants with lower baseline ppFEV1. These findings support measurable physiological benefit from ETI across a broad spectrum of baseline lung function, while highlighting the need for longer-term studies of outcomes in people with near-normal spirometry.
Background/Objectives: Glaucoma is a progressive optic neuropathy characterized by retinal ganglion cell loss and visual field deterioration despite adequate intraocular pressure control. Neuroprotective adjunct therapies have therefore been investigated, and citicoline has emerged as a potential candidate. We conducted a systematic review to summarize and critically appraise the evidence on the effects of citicoline, used as an adjunctive therapy, on visual function, functional vision, and quality of life in patients with glaucoma. Methods: A systematic literature search was performed in major electronic databases (PubMed, Scopus, and Web of Science) following PRISMA guidelines. Randomized and non-randomized clinical studies evaluating citicoline as adjunctive therapy in glaucoma were included. Outcomes of interest comprised visual function, electrophysiology, structural optical coherence tomography parameters, quality of life, and safety. Risk of bias was assessed using RoB 2 and ROBINS-I tools. Results: Fifteen studies were included in this review, ten randomized controlled trials and five non-randomized clinical trials. Included studies showed heterogeneous designs and follow-up durations. Several studies reported improvements in electrophysiological responses, including retinal and post-retinal functional markers, and relative stabilization of selected visual field indices, with some studies reporting preservation of retinal nerve fiber layer and ganglion cell complex thickness under stable intraocular pressure. However, these surrogate outcomes were not consistently accompanied by improvements in visual acuity or patient-reported quality-of-life measures. Methodological limitations and endpoint variability reduced comparability across studies. Across oral, topical, and intramuscular routes of administration, citicoline was generally reported to have a favorable safety and tolerability profile. Conclusions: Current evidence suggests that citicoline may exert neurobiological effects compatible with neuroprotection in glaucoma, but the clinical significance of these findings remains uncertain. Available data are insufficient to support routine clinical recommendation. Well-designed randomized trials with standardized, patient-relevant outcomes are required to determine whether these effects translate into meaningful visual benefit.
Background: Glucocorticoids (GCs) remain the cornerstone of polymyalgia rheumatica (PMR) management, but their cumulative toxicity necessitates effective GC-sparing strategies. Recent randomized controlled trials (RCTs) evaluating targeted therapies with diverse mechanisms of action have offered an unprecedented opportunity to dissect the disease’s underlying immunobiological architecture. Methods: A focused narrative literature search was conducted within PubMed to analyze Phase 2 and Phase 3 RCTs and long-term extension studies investigating Janus Kinase (JAK) inhibitors, secukinumab (anti-IL-17A), abatacept, anti-CD20 monoclonal antibody rituximab, and anti-IL-6 receptor (IL-6R) antagonists in PMR patients. Results: This scoping analysis highlighted how distinct molecular pathways demonstrated highly divergent efficacy profiles. Specifically, baricitinib and tofacitinib (two JAK inhibitors), along with sarilumab and tocilizumab (anti-IL-6 receptor), achieved robust short-term clinical response and acute-phase reactant normalization, though anti-IL-6 receptor extension data revealed persistent localized musculoskeletal symptoms in a patient subgroup. In chronic, relapsing, GC-dependent settings, the anti-IL-17a monoclonal antibody secukinumab significantly increased sustained GC-free remission. The placebo-controlled Phase 2 BRIDGE-PMR trial and its subsequent 1-year extension study demonstrated the efficacy of a single intravenous infusion of rituximab: a significantly higher rate of sustained, GC-free clinical remission was observed compared to the placebo group. Conversely, the T-cell co-stimulation modulator abatacept failed to demonstrate significant therapeutic efficacy. All these high-impact trials confirmed that precision cytokine and cellular targeting could provide a safe and highly tolerable alternative to conventional GC management. Methodologically, however, some of these trials had a primary limitation, and this was the reliance on short-term 24-week endpoints, which introduced a critical “temporal blind spot” that masked late relapses during advanced GC tapering. Conclusions: PMR is hypothesized to represent a complex syndrome of compartmentalized phenotypic convergence, where distinct molecular axes could drive pathology across different chronological stages (modeled as an acute/IL-6-driven phase vs. a chronic/Th17-dependent phase). While these therapeutic differences suggest a novel conceptual framework, head-to-head comparative research is strictly required to establish clear clinical hierarchies. In addition, upcoming clinical trial designs should systematically extend evaluation periods to 52 weeks to accurately assess sustained remission and differentiate between short-term suppression and long-term therapeutic efficacy.
Background/Objectives: Kienböck disease (idiopathic avascular necrosis of the lunate) is treated almost exclusively surgically; its pharmacological evidence base comprises fewer than five primary publications and ~20 patient-level observations. Femoral-head, jaw, and knee osteonecrosis have decades of evidence, including randomised trials. We ask whether extra-carpal evidence can be translated to Kienböck disease and the wider Carpal Avascular Necrosis Family (lunate, scaphoid/Preiser, capitate, hamate, triquetrum). Methods: We conducted a narrative review reported per SANRA, searching PubMed, CrossRef, Google Scholar and three specialty registries from inception to 2026 across eleven drug classes and eleven skeletal sites. All references were independently verified against primary sources (PubMed/CrossRef). No Kienböck-specific randomised or controlled data exist; all conclusions therefore rest on indirect, extra-carpal evidence. Results: Three pathways (subchondral insufficiency fracture, microvascular ischaemia, hypercoagulability) predict drug-class plausibility differently by site. Iloprost is the candidate most consistently aligned across the translation axes, though no direct lunate data exist; teriparatide provides the only randomised evidence suggesting reversal of established osteonecrosis at any site (medication-related osteonecrosis of the jaw). The lunate sits within a coherent carpal AVN family sharing end-arterial supply, Lichtman-grade trajectories, and a near-identical evidence vacuum. Conclusions: A Four-Axis Translation Framework (mechanistic alignment, anatomic concordance, Lichtman-stage applicability, lunate-specific risk–benefit geometry) is proposed to evaluate which extra-carpal evidence is admissible at the lunate; with the carpal AVN family construct, these are the review’s two novel contributions.
