Purpose Trigger finger is typically managed with corticosteroid injections followed by surgical release if injections fail. Office-based ultrasound-guided percutaneous A1 pulley release (USGPR) has emerged as a contemporary alternative that provides definitive surgical treatment in office settings, potentially eliminating both the recurrence risk of injections and the facility costs of traditional surgery. However, USGPR device costs and cost-effectiveness remain uncertain. Prior cost-effectiveness analyses do not include USGPR as a comparator and use reimbursement data from 2016 and earlier that may not reflect contemporary payment structures. This study evaluated the cost-effectiveness of contemporary trigger finger treatment strategies, including office-based USGPR, from a Medicare payer perspective using current 2025 reimbursement data and determined device cost thresholds at which USGPR becomes cost-effective. Methods A decision-tree cost-effectiveness analysis was performed over a 1-year time horizon comparing five strategies: up to one, two, or three corticosteroid injections followed by facility-based open A1 pulley release if needed; immediate facility-based open release; and immediate office-based USGPR. Costs were derived from 2025 Medicare reimbursement data. Effectiveness was expressed as quality-adjusted life-years. Deterministic, threshold, and probabilistic sensitivity analyses were performed. Results The three-injection strategy was most cost-effective, with expected costs of $513 and net monetary benefit of $39,687 at a willingness-to-pay threshold of $50,000 per quality-adjusted life-year. Probabilistic sensitivity analysis demonstrated this strategy remained cost-effective in 100% of 10,000 simulations. At the base case device cost of $800, office-based USGPR was most expensive at $1,577. However, threshold analyses demonstrated that USGPR would become cost-effective at device costs below $232 relative to the three-injection strategy and below $519 relative to immediate facility-based open release. Conclusions Offering up to three corticosteroid injections before surgical release represents the most cost-effective contemporary strategy for trigger finger management from a current Medicare payer perspective. At current device costs, office-based USGPR is not cost-effective, but substantial opportunity exists for this technique to become cost competitive as device costs decline. Type of study/level of evidence Economic and Decision Analysis II.
Since the trabecular meshwork (TM) is central to intraocular pressure (IOP) regulation and glaucoma, a deeper understanding of its genomic landscape is needed. We present a multimodal, single-cell resolution analysis of mouse limbal cells (includes TM). In total, we sequenced 9,394 wild-type TM cell transcriptomes. We discovered three TM cell subtypes with characteristic signature genes validated by immunofluorescence on tissue sections and whole-mounts. The subtypes are robust, being detected in datasets for two diverse mouse strains and in independent data from two institutions. Results show compartmentalized enrichment of critical pathways in specific TM cell subtypes. Distinctive signatures include increased expression of genes responsible for (1) extracellular matrix structure and metabolism (TM1 subtype), (2) secreted ligand signaling to support Schlemm’s canal cells (TM2), and (3) contractile and mitochondrial/metabolic activity (TM3). ATAC-sequencing data identified active transcription factors in TM cells, including LMX1B. Mutations in LMX1B cause high IOP and glaucoma. LMX1B is emerging as a key transcription factor for normal mitochondrial function, and its expression is much higher in TM3 cells than other limbal cells. To understand the role of LMX1B in TM function and glaucoma, we single-cell sequenced limbal cells from Lmx1bV265D/+ mutant mice (2491 TM cells). In Lmx1bV265D/+ mice, TM3 cells were uniquely affected by pronounced mitochondrial pathway changes. Mitochondria in TM cells of Lmx1bV265D/+ mice are swollen with a reduced cristae area, further supporting a role for mitochondrial dysfunction in the initiation of IOP elevation in these mice. Importantly, treatment with vitamin B3 (nicotinamide), which enhances mitochondrial function and metabolic resilience in other contexts, significantly protected Lmx1b mutant mice from IOP elevation.
Sepsis is defined as a dysregulated host response to infection that leads to life-threatening organ dysfunction. The infectious insult triggers a dysregulated immune response that variably activates and suppresses multiple body system functions. Susceptibility to either developing or succumbing to sepsis is influenced by pathogen load and virulence; site of infection; host factors, including genetics, biological variability, comorbidities, immunosuppression, and extremes of age; and a wide range of external influences, such as social deprivation and local environment. Increasing appreciation of the underlying pathobiology has identified differing biological signatures with variable temporal evolution. This variability highlights the requirement to individualise treatment with targeted interventions guided by rapidly accessible biomarkers. Although improved outcomes have been obtained with better prevention, early recognition, and treatment, sepsis is a major cause of global mortality and morbidity. All populations having the benefits currently enjoyed by a privileged few is imperative. This Seminar aims to unravel the complexity of the condition, describing epidemiology and pathophysiology, evolving fundamental shifts, patient management, current challenges, and future developments.
To holistically understand the biology of animals, we must unravel the complexities and specificities of host-microbe interactions across animal taxa. Birds represent enigmatic and scientifically compelling hosts in which to understand these interactions. Here, we present a brief summary of a series of conversations among avian microbiome researchers regarding methodological challenges facing the avian microbiome field, where most research to date has focused on bacterial communities of the gut. Collectively, we acknowledged a commonly shared but underreported issue facing the avian microbiome field: that of difficulty in obtaining high-quality and high-yield microbial DNA from avian fecal samples. We discuss some of the potential reasons underlying low DNA yields, such as inhibitory compounds and rapid DNA degradation, and provide recommendations for how researchers in the avian microbiome field might cope with these methodological challenges. Collective and dedicated efforts to address these challenges will be required for a robust understanding of host-microbe interactions in avian systems.
Chemical weathering produces alkalinity that, in conjunction with marine carbonate burial, mediates the return of carbon from planetary volcanism, metamorphism, and sedimentary recycling. However, clay formation during chemical denudation can result in reduced alkalinity fluxes. Because the 7Li/6Li ratio of dissolved lithium in river water (S7Liriver) traces the degree of clay mineral formation following silicate dissolution at the watershed scale, fluvial Li isotope ratios and their expression in sedimentary archives can potentially convey the strength of silicate weathering-driven CO2 drawdown. However, little attention has been given to the coupled dynamics that emerge when also considering the weathering of coexisting non-silicate minerals, such as carbonate and sulfide phases, that also modify alkalinity and carbon fluxes to the global ocean-atmosphere system. These additional phases potentially complicate attempts to relate S7Liriver values to changes in the partial pressure of atmospheric carbon dioxide (pCO2). Here we address this complexity by compiling a global dataset of S7Liriver values and major and trace ion concentrations (n = 413), attributing solutes among lithologic sources and clay sinks with the MEANDIR inversion model and comparing numerical results to watershed properties. The analyses demonstrate that S7Liriver values correlate with alkalinity consumption by clay formation but do not simply relate to the net impact of weathering on atmospheric pCO2 due to the weathering of carbonate and sulfide minerals. However, other weathering indices, like river Li/Na ratios, may more directly relate to pCO2 change. A simple regolith model demonstrates that mineral supply, driven by bedrock composition and uplift, impacts the balance of sulfuric and carbonic acid weathering, the degree of clay mineral formation, and the fraction of Li incorporated from solution into clays. As a result, where measured or calculated S7Liriver trends have previously been interpreted in terms of clay mineral formation, we interpret S7Liriver as reflecting mineral supply modulated by climate.
