Search Results (568)

Background/Objectives: Abnormal muscle tone and impaired motor control commonly limit gait recovery after stroke. Robot-assisted gait training has been introduced to augment conventional rehabilitation; however, its effects on stage-based motor recovery, functional ambulation, and muscle tone during the subacute phase remain unclear. Methods: This prospective, single-center, randomized controlled trial enrolled 30 patients with subacute stroke who received robot-assisted gait training plus conventional rehabilitation (R-BoT Plus group, n = 15) or conventional rehabilitation alone (control group, n = 15) over 4 weeks. The primary outcome was the change in Brunnstrom recovery stage of the lower extremities (BRS-LE). Secondary outcomes included Functional Ambulation Category (FAC), Fugl–Meyer Assessment for the Lower Extremity (FMA-LE), clinical spasticity measures (Modified Ashworth Scale and Modified Tardieu Scale), and muscle mechanical properties (MyotonPRO). Exploratory analyses were conducted to examine the associations between changes in stage-based motor recovery (ΔBRS-LE), functional ambulation (ΔFAC), and MyotonPRO parameters. Within-group changes were assessed using the Wilcoxon signed-rank test. Between-group effects were primarily evaluated using baseline-adjusted ANCOVA with HC3 robust standard errors, with Wilcoxon rank-sum tests on change scores as sensitivity analyses. Associations between changes in clinical outcomes and MyotonPRO parameters were evaluated using Spearman’s rank correlation coefficient (ρ). Results: BRS-LE (p = 0.014) and functional ambulation (p = 0.041) were significantly improved in the R-BoT Plus group. Changes in FMA-LE and clinical spasticity measures did not differ significantly between groups. Quantitative myotonometry revealed selective muscle- and parameter-specific changes. No robust correlations were observed between MyotonPRO parameters and changes in BRS-LE. Conclusions: The addition of robot-assisted gait training to conventional rehabilitation was associated with greater improvements in stage-based lower-limb motor recovery and functional ambulation in patients with subacute stroke. In contrast, cumulative impairment scores and conventional clinical spasticity measures demonstrated limited changes between groups. Quantitative muscle mechanical assessment revealed selective muscle-specific adaptations, supporting its role as a complementary tool for mechanistic characterization rather than as a surrogate marker of motor recovery. Future studies incorporating dose-matched designs and longer follow-up periods are warranted to clarify the independent and long-term effects of robot-assisted gait training. Full article

In this study, pristine biochar (BC1) and magnesium-modified biochar (BC2) were prepared from corn straw. Different nitrogen deposition intensities (0, 8, 30, and 50 kg N/(ha·yr)) were simulated by adding NH₄NO₃ solution. A laboratory incubation experiment was conducted to investigate the effects of biochar addition and N deposition on CO₂ emissions, CH₄ uptake, and microbial community structure in soils from a temperate mixed conifer–broadleaf forest. The results showed that BC1 significantly increased cumulative CO₂ emissions (p < 0.05), while no significant difference was observed between BC2 and the control. N deposition had no significant effect on CO₂ emissions. Biochar addition significantly promoted cumulative CH₄ uptake (p < 0.05), with BC2 exhibiting a stronger promoting effect than BC1. In contrast, N deposition significantly inhibited CH₄ uptake (p < 0.05) in a dose-dependent manner. Spearman’s correlation analysis revealed that cumulative CO₂ emissions were significantly or highly significantly negatively correlated with the relative abundances of Elusimicrobiota, Actinomycetota, Chloroflexota, Planctomycetota, Acidibacter, Bacillus, Paenibacillus, Acidothermus, and Mycobacterium, and significantly positively correlated with Bacteroidota, Bdellovibrionota, Pseudomonadota, Devosia, and Mesorhizobium. Cumulative CH₄ uptake was highly significantly positively correlated with the relative abundance of Bacteroidota and significantly negatively correlated with Chloroflexota, Candidatus_Eremiobacterota, and Mycobacterium. These findings demonstrate that N deposition has no significant impact on soil CO₂ emissions but significantly inhibits CH₄ uptake, while magnesium-modified corn straw biochar promotes CH₄ uptake without substantially increasing CO₂ emissions, highlighting its promising application potential. Full article

Glucocorticoids (GCs) are widely used for their potent anti-inflammatory and immunosuppressive effects, but their use is strongly associated with negative impacts on bone health. Rapid bone loss and an increased risk of fragility fractures are characteristics of glucocorticoid-induced osteoporosis (GIOP), the most common type of secondary osteoporosis. While oral GCs are a well-known cause of GIOP, growing evidence suggests that non-oral routes of administration may also negatively affect the skeleton. This review summarizes current knowledge on the pathophysiology of GIOP, highlighting the complex relationship between direct and indirect mechanisms. It examines the effects of various routes of GC administration—oral, intravenous, inhaled, topical, and epidural—on bone mineral density, microarchitecture, and fracture. While parenteral GCs may have fewer systemic effects than oral therapy, long-term exposure or high cumulative doses may still cause clinically significant skeletal deterioration. This review also discusses current methods for assessing, preventing, and treating the fracture risk associated with GIOP. These strategies include lifestyle modifications, calcium and vitamin D supplements, and medications such as denosumab, bisphosphonates, and anabolic agents. Reducing the incidence of glucocorticoid-associated fractures and improving prevention and treatment requires an understanding of how GCs impact bone. Full article

Background: Active surveillance of small renal masses is challenged by cumulative radiation exposure from repeated CT imaging, raising long-term health concerns. Low-dose CT protocols offer a strategy to mitigate this risk but are limited by uncertainty regarding measurement accuracy and potential effects on clinical decision-making. Methods: We propose an uncertainty-aware analytical framework using a multi-observer dataset of 40 paired CT cases (low-dose vs. standard-dose). The methodology combines statistical agreement assessment (concordance correlation coefficient, intraclass correlation coefficient), multi-algorithm machine learning prediction (linear regression, random forest, gradient boosting, and SVR), and integrated uncertainty quantification to evaluate equivalence across imaging protocols. Results: Comparative analysis demonstrates near-perfect concordance between protocols (concordance correlation coefficient = 0.9930). Linear regression achieved the highest predictive performance (R² = 0.9933, MAE = 0.4239 mm, MAPE = 2.07%), outperforming more complex ensemble models, highlighting that interpretable models can achieve superior accuracy without compromising reliability. Conclusions: Clinically, the framework supports the safe adoption of low-dose CT for longitudinal tumor assessment, preserving measurement fidelity and diagnostic confidence essential for timely intervention or continued surveillance. Radiologically, it ensures robust lesion characterization across protocols while minimizing cumulative radiation exposure, particularly in younger patients. By integrating uncertainty quantification, this approach enhances transparency, informs clinical decision-making, and facilitates personalized, evidence-based surveillance strategies, promoting safer, dose-optimized imaging in the management of small renal masses. Full article

Background: Statins are central to primary and secondary prevention of atherosclerotic cardiovascular disease but are often underutilized due to myopathy and intolerance. While individual pharmacogenetic (PGx) variants, particularly in SLCO1B1, are linked to statin-associated muscle symptoms, the real-world impact of both clinical and cumulative PGx burden on regimen modification and adverse outcomes remains unclear. We aimed to evaluate the existing uncertainty regarding whether combined PGx scores can effectively guide statin dose titration and regimen modification, thereby filling a key clinical gap. Methods: A retrospective cohort study of 911 statin-treated patients with coronary artery disease was conducted from the Qatar Cardiovascular Biorepository with available whole-genome sequencing data. Variants in SLCO1B1, ABCG2, and CYP2C9 were combined into a functional PGx burden score, and their associations with statin regimen modification, intolerance, myopathy, liver injury, adherence, and composite adverse events were evaluated. The composite adverse events were defined as the occurrence of any statin-related adverse event, including statin-associated myopathy, liver injury, or poor medication adherence, during the follow-up period. Patients were classified as having experienced the composite outcome if at least one of these events occurred. Results: Over 12 months following statin initiation, 10.2% of patients underwent dose escalation, 11.4% de-escalation, and 78.4% remained on the same regimen. PGx burden is not statistically significantly associated with statin intolerance (OR 1.14; 95% CI: 0.73–1.76), composite adverse outcome (OR 1.08; 95% CI 0.82–1.42), or time to regimen change (HR 1.02; 95% CI 0.77–1.35). However, higher PGx burden showed a directional tendency toward dose de-escalation (RRR 1.18, 95% CI 0.76–1.84) and lower likelihood of escalation (RRR 0.93, 95% CI 0.56–1.54). Conclusions: Clinical factors, particularly statin intensity and myopathy, were the primary determinants of regimen modification. The PGx burden contributes to vulnerability to statin-related adverse effects in a context-dependent manner but does not independently drive statin regimen modification in routine clinical practice. Prospective studies are warranted to assess the clinical utility of PGx-guided workflows in statin therapy. Full article

Background/Objectives: Ibrutinib has significantly improved outcomes in chronic lymphocytic leukemia (CLL), but evidence from real-world settings on the impact of early dose modifications and consequent relative dose intensity (RDI) maintenance on survival outcomes is limited. This study evaluated the impact of dose reductions and RDI maintenance during the first 90 days of treatment on clinical outcomes in patients with CLL receiving ibrutinib in routine clinical practice. Methods: A post hoc analysis of the prospective observational EVIdeNCE study (NCT03720561) was conducted, including 275 patients with CLL treated with ibrutinib. Baseline clinical and biological factors associated with early dose modifications and RDI maintenance over the first 90 days were analyzed. Cox proportional hazards models, adjusted for disease- and patient-related covariates, were applied to assess associations with overall survival (OS) and progression-free survival (PFS), using a landmark approach to control for immortal time bias. Results: Patients with higher comorbidity burden—indicated by higher Cumulative Illness Rating Scale scores and poorer ECOG performance status—were more likely to undergo early dose reductions. RDI declined slightly over 90 days, but most patients maintained ≥80% of their RDI. The impact of disease-risk factors appeared more clearly when assessing the relationship between 100% RDI at 90 days and PFS, with ibrutinib at 100% RDI associated with improved PFS (hazard ratio, HR 2.26, 95% confidence interval, CI: 1.23–4.15). However, after adjusting for patient characteristics (e.g., comorbidity burden and cardiovascular history), the 100% RDI rate no longer showed a statistically significant effect on PFS (HR 1.84, 95% CI: 0.93–3.63). Conclusions: Baseline comorbidities and functional status drive early dose modifications, but these adjustments and RDI variability do not independently impact survival outcomes, confirming the overall tolerability of ibrutinib in real-world CLL management. Full article

Background: Continuity of care for rheumatoid arthritis patients within regional networks enables stable long-term clinical data collection, despite chronic rheumatologist shortages in Japan. We determined 5-year drug survival and discontinuation reasons for eight biological disease-modifying antirheumatic drugs (bDMARDs) using a regional multicenter registry. Methods: We retrospectively analyzed 1182 patients initiating their first (naïve, n = 784) or subsequent (switch, n = 398) bDMARD between May 2001 and August 2022 across five institutions. The primary endpoint (5-year drug survival) and secondary endpoints (discontinuation risk factors and cumulative incidence of reasons) were evaluated using Kaplan–Meier curves, Cox proportional hazards, and Fine & Gray models. Results: Baseline characteristics varied significantly among bDMARDs. Five-year drug survival in the naïve cohort ranged from tocilizumab (50.8%) to golimumab (22.6%); in the switch cohort, from abatacept (42.6%) to infliximab (10.0%). In multivariable Cox analysis of naïve patients, male sex (hazard ratio [HR] = 1.49, 95% confidence interval [CI] = 1.09–2.02), lower baseline 28-joint Disease Activity Score with erythrocyte sedimentation rate (DAS28-ESR) (HR = 0.90, 95% CI = 0.82–0.99), and absence of methotrexate co-therapy (HR = 0.73, 95% CI = 0.55–0.97) predicted discontinuation. The lower baseline DAS28-ESR association potentially reflects successful courses toward intentional cessation following remission. Discontinuations were attributed to inadequate response (27.1%), non-adverse events (25.3%), and adverse events (17.3%). Conclusions: Tocilizumab and abatacept demonstrated the highest retention rates in biologic-naïve and switch cohorts, respectively. Early, individualized drug selection and dose optimization are crucial to maximizing long-term bDMARD effectiveness before switching. Full article

Background: Exercise interventions are commonly considered as non-pharmacological approaches to support cognitive and functional outcomes in older adults with dementia. However, the effects reported in the literature remain heterogeneous, and commonly used time-based dose markers may be insufficient to explain variability across trials. Methods: A systematic review and meta-analysis of randomized controlled trials was conducted in accordance with PRISMA 2020 guidelines. Eligible trials described benefits with cognitive, functional or behavioral changes associated with structured exercise interventions in older adults with dementia. Random-effects meta-analysis and meta-regression models were used to derive pooled effects and assess if linear dose indicators (e.g., duration of intervention, session length, frequency and total cumulative dose) reflected heterogeneity. Results: Twenty-two studies were analyzed. Based on our pooled analyses, a small but statistically significant improvement was observed under the fixed-effects model (g = 0.106, 95% CI 0.015–0.197; p = 0.023), but this was not significant for random-effects models (g = 0.117, 95% CI −0.021–0.254; p = 0.097), while suggesting moderate between-study heterogeneity (Q(21) = 43.530, p = 0.003; I² = 51.757%; τ² = 0.052). For the main random-effects meta-regression, standard linear dose indicators did not significantly explain between-study heterogeneity (Qm(3) = 1.06, p = 0.7867; R²_analog ≈ 0), while significant residual heterogeneity remained (I² ≈ 56.03%). Conclusions: In the literature so far, there are limited and heterogeneous effects of exercise interventions on cognition and functions in older adults with dementia. These findings in all literature suggest that the current evidence does not support a consistent linear dose–response relationship but rather will likely depend to some extent on feasibility and supervision (again, quality of the interventions), thus emphasizing that exercise strategies must be contextually sensitive rather than dose-dependent. Full article

The behavior of phosphorus (P) fertilizers in soil is governed not only by fertilizer solubility, but also by P mobility and vertical redistribution within the soil profile under contrasting water regime. This study aimed to investigate the combined effects of water regime, fertilizer type, and soil properties on the vertical redistribution of ammonium acetate–lactate extractable phosphorus (P-AL) in the surface soil layer under controlled pot conditions. Experiments were conducted using three soils with contrasting chemical properties: AC-LO (acidic loam, pH 5.9), NE-CL (neutral clay loam, pH 6.8), and AL-SL (alkaline sandy loam, pH 8.0). Four simulated rainfall regimes were applied at a constant rate of 25 mm day⁻¹, corresponding to cumulative water inputs of 0 mm (W0), 50 mm (W50), 100 mm (W100), and 150 mm (W150). Fertilizer treatments included an unfertilized control (NF), a liquid NP 4–18 fertilizer applied at a low dose (L1), a liquid NP 4–18 fertilizer applied at a high dose (L2), and a solid NPK 15–15–15 fertilizer (S). Water regime exerted the strongest control on P mobility, with P-AL increasing by approximately 40–60% from W0 to W150, depending on soil type. In AC-LO, strong P fixation under low moisture minimized differences among fertilizer treatments, whereas under higher moisture (W100–W150), liquid fertilizers—particularly L2—resulted in P-AL levels approximately 10–30% higher than those of the solid fertilizer. In NE-CL, P mobility was moderate and, under W100–W150, L2 produced P-AL values approximately 10–15% higher than the solid fertilizer, promoting a more uniform P redistribution within the 2–8 cm layer. In AL-SL, the response under wet conditions depended on the water regime: at W100, L2 generated P-AL values comparable to the solid fertilizer, whereas at W150, L2 increased P-AL by approximately 11% relative to the solid form. Overall, the results indicate that soil chemical properties primarily regulate the extent of phosphorus redistribution, while water regime controls its intensity and fertilizer form influences the initial spatial configuration of P within the surface soil layer. The findings provide mechanistic insight into short-range phosphorus transport in soil, without allowing direct inferences regarding agronomic efficiency or crop response. Full article

Urinary gluten immunogenic peptides (u-GIPs) have been proposed as a complementary marker to classical intestinal permeability tests based on lactulose, mannitol, and the lactulose:mannitol ratio (LMR). However, the effects of gluten dose, urine collection interval, and sampling strategy on their performance remain insufficiently defined. This study evaluated these variables to support protocol standardization. Data from four standardized protocols including 46 healthy adults exposed to 0, 2, 4, or 10 g of gluten were analyzed. All participants ingested fixed doses of lactulose and mannitol. Urine was collected cumulatively (0–6 h and 0–15 h) or by individual voids. u-GIP levels were measured by lateral-flow immunoassay, and lactulose and mannitol by ion chromatography. u-GIP excretion showed a clear dose dependence. Lactulose excretion increased transiently only at the 10 g dose during the 0–6 h interval, while mannitol excretion and LMR were unaffected. The u-GIP excretion index showed linear proportionality at the 2 g and 4 g doses but exhibited saturation kinetics at the 10 g dose. The 4 g dose showed the lowest interindividual variability. Sampling strategies yielded equivalent results. A 4 g gluten challenge combined with a 6 h urine collection demonstrated effectiveness in healthy volunteers and may be suitable for clinical application. Further research involving larger cohorts of both healthy individuals and patients with intestinal hyperpermeability is required to validate this method. Full article

Bipolar junction transistors (BJTs) are susceptible to total ionizing dose (TID) effects in radiation environments, leading to current gain degradation. Addressing the initial-value sensitivity issue in solving the two-dimensional implicit coupled equations within the BJT transceiver current analytical model based on symmetric double-gate MOSFET surface potential theory, this study proposes a machine learning-based BJT surface potential prediction method. This method integrates a classification model, a sample generation model, and a regression model to achieve accurate prediction of BJT surface potential under TID damage. For the sample generation model, a residual Transformer variational autoencoder is designed to enhance the efficiency of generating effective samples. For the regression model, a dynamic exponential weighted mean squared error function is adopted as the loss function for XGBoost to improve the model’s generalization capability. Simulation results demonstrate that at cumulative total doses of 50 and 100 krad(Si), the average relative error between predicted over-base currents and irradiation test results is as low as 0.1847 and 0.2619, respectively, confirming the accuracy of the proposed prediction method. Full article

Background: Low-dose computed tomography (LDCT) screening reduces lung cancer mortality; however, the effectiveness of screening programs depends not only on detection, but also on completion of downstream diagnostic pathways following a positive screening result. Refusal of recommended invasive diagnostic procedures represents a critical but understudied form of post-screening attrition. Methods: This retrospective observational study was conducted within an organized multicenter LDCT lung cancer screening program in Vojvodina, Serbia. Consecutive participants screened between September 2020 and October 2025 were included. Positive screening was defined as Lung-RADS 4A, 4B, or 4X. Refusal was defined as the absence of any invasive diagnostic procedure within six months following multidisciplinary team recommendation. Demographic, clinical, smoking-related, and perceptual factors were analyzed. Time to invasive diagnostic procedures was assessed for bronchoscopy and surgical treatment. Multivariable logistic regression was used to identify factors independently associated with refusal. Results: Among 10,261 screened individuals, 479 (4.7%) had positive LDCT findings. Of these, 60 participants (12.5%) refused invasive diagnostic evaluation. In multivariable analysis, multimorbidity (OR 3.45, 95% CI 1.61–7.38), previous malignancy (OR 2.92, 95% CI 1.16–7.35), higher cumulative smoking exposure (OR 1.02 per pack-year, 95% CI 1.00–1.03), and screening center (Subotica vs. Novi Sad: OR 2.40, 95% CI 1.21–4.78) were independently associated with refusal of invasive diagnostic procedures. Greater concern about personal lung cancer risk was associated with a lower likelihood of refusal (OR 0.54, 95% CI 0.29–0.99). Time to bronchoscopy differed significantly across screening centers and screening years, whereas time to surgical treatment was comparable across centers and years. Conclusions: Refusal of invasive diagnostic procedures following positive LDCT screening represents a meaningful implementation challenge influenced by both patient vulnerability and system-level factors. Addressing modifiable barriers through improved risk communication and optimization of post-screening diagnostic pathways may enhance diagnostic continuity and strengthen the real-world effectiveness of lung cancer screening programs. Full article

Background/Objectives: Treatment with immune checkpoint inhibitors (ICIs) in patients with advanced melanoma has greatly improved clinical outcomes but can induce immune-related adverse events (irAEs). ICI-induced immune-related (ir) colitis is one of the most common severe irAEs and is primarily managed by treatment with high-dose corticosteroids. Some patients are steroid-refractory and require additional immunosuppressants. Infliximab is commonly used as the additional treatment of choice, while data for other immunosuppressants such as mycophenolate mofetil (MMF) are sparse. Methods: We used MMF to treat ir colitis in a cohort of patients in Heidelberg and compared clinical data with patients who received standard irAE management with infliximab in the Cancer Centers of Heidelberg, Hannover, Mainz, and Kiel. Outcome measures included response rate, time to response, duration and amount of steroid intake, and recurrence of colitis, as well as progression-free survival (PFS) and overall survival (OS) measured from the start of steroid intake. Results: Out of 52 patients refractory to steroids, 31 were treated with additional MMF and 21 with additional infliximab. A total of 24 out of 31 patients (77.4%) experienced bowel habit normalization during treatment with MMF after a median of seven days. Seven patients required additional infliximab to achieve a resolution of symptoms. Twenty out of 21 patients (95.2%) showed a normalization of stool frequency with infliximab after a median of eleven days. One patient required additional MMF to achieve a normal bowel habit. Hence, resolution of symptoms was achieved during both treatment regimens (p = 0.081) in a comparable period of time (p = 0.858). Neither recurrence of colitis after additional immunosuppression (p = 0.760) nor rate of CMV positivity after recurrence of colitis (p = 0.898) differed between groups. We observed a tendency towards longer treatment duration (108 vs. 85 days, p = 0.052) and significantly higher cumulative corticosteroid intake (7585 mg vs. 3485 mg, p = 0.002) in the MMF group compared to the infliximab group. However, we observed significantly higher cumulative steroid intake and a longer duration of corticosteroid therapy in patients treated at the Heidelberg center compared with those treated at the other participating centers within the infliximab group. In contrast, no significant differences in corticosteroid duration or cumulative dose were observed in the center-internal comparison between MMF- and infliximab-treated patients at Heidelberg. These subgroup analyses may indicate that the observed differences in corticosteroid exposure are more likely related to center-specific management strategies rather than substance-specific effects. Neither median PFS nor OS differed between the groups (mPFS: MMF: 3.2 months; infliximab: 2.1 months (p = 0.978); mOS MMF: 12 months; infliximab: 9.5 months (p = 0.561)). Conclusions: The data point to MMF as a well-tolerated, oral treatment alternative for patients with ICI-induced ir colitis, especially in patients where infliximab is contra-indicated. Full article

Background/Objectives: Reproducible evaluation of aerosol dispersibility remains a key challenge in the development of dry powder inhalers (DPIs), where small variations in particle cohesion, morphology, or device resistance can lead to large differences in aerodynamic performance. In passive DPIs, the forces required for powder fluidization and aerosolization arise from the interaction of patient inspiratory airflow with device geometry and must overcome strong interparticle cohesive forces to enable effective lung delivery. Cascade impaction is the gold standard for determining aerodynamic particle size distribution (APSD), but its low throughput and experimental burden limit its utility for systematic formulation and device screening. Prior studies have explored laser diffraction-based particle sizing under varying dispersion energies as indirect metrics of powder dispersibility. Here, we extend this approach by introducing a mathematically rigorous, distribution-based framework that applies the first-order Wasserstein distance (Earth Mover’s Distance) to quantify relative dispersibility with respect to a material-specific maximally dispersed reference state. Methods: Mannitol, trehalose, and inulin were spray-dried under matched conditions to generate model dry powders. Particle size distributions were measured by laser diffraction (Sympatec HELOS/R) using both a RODOS dry dispersion module to define a maximally dispersed reference state and an INHALER module to generate aerosols under clinically relevant dispersion conditions spanning multiple device resistances and pressure drops. For each condition, the Wasserstein-1 distance (W₁) was computed between cumulative volume-based size distributions obtained under reference and inhaler-based dispersion. Cascade impaction was used as an orthogonal method to characterize aerodynamic performance under a representative dispersion condition. Results: W₁ captured formulation-, device-, and flow-dependent differences in dispersibility that were not readily separable by visual inspection of particle size distributions alone. Crystalline mannitol exhibited the largest and most flow-rate-dependent W₁ values, whereas amorphous trehalose and polymeric inulin showed smaller W₁ values with distinct, non-monotonic pressure responses that depended on device resistance. W₁ qualitatively aligned with cascade impaction metrics, exhibiting a positive association with mass median aerodynamic diameter and an inverse association with fine particle fraction, while also demonstrating that efficient dose emission can occur despite incomplete deagglomeration. Conclusions: This study establishes the Wasserstein distance as a physically interpretable, formulation-agnostic metric for quantifying aerosol dispersibility relative to a material-specific reference state. This framework enables systematic comparison of dispersion efficiency across devices and operating conditions using standard laser diffraction data and provides a reproducible basis for mechanistic optimization of DPI formulations and inhaler designs. Full article

Background and Objectives: The use of fluoroscopy during retrograde intrarenal surgery (RIRS) results in cumulative ionizing radiation exposure to both the patient and the surgical team. We aimed to evaluate the efficacy and safety of fluoroscopy-free (FF) RIRS performed by experienced surgeons in the management of renal stones < 2 cm. Materials and Methods: A total of 255 patients who underwent RIRS for renal stones < 2 cm between 2023 and 2025 were retrospectively analyzed. Patients were randomly assigned to the groups. Fluoroscopy was used (FU) during RIRS in 123 patients, whereas fluoroscopy was not used during RIRS in 132 patients. All procedures were performed by a single experienced surgeon. For patients in both groups, the following variables were retrospectively reviewed: demographic characteristics, stone characteristics, localization, and diameter, operative time, fluoroscopy time and dose, postoperative complications, length of hospital stay, and stone-free rates (SFR). Results: The operative time was 34.7 ± 8.7 min in the FF group and 42.0 ± 12.9 min in the FU group, being significantly shorter in the FF group (p < 0.001). No fluoroscopy was used in the FF group, whereas in the FU group the fluoroscopy time and dose were recorded as 7.75 ± 3.6 s and 1.31 ± 0.61 mGy, respectively. There were no significant differences between the groups in terms of length of hospital stay or SFR. No intraoperative complications were observed in either group. Postoperative complications occurred in 29 (21.9%) patients in the FF group and 42 (34.1%) patients in the FU group; the difference between groups was statistically significant (p = 0.030). Conclusions: In appropriately selected patients with renal stones < 2 cm, fluoroscopy-free RIRS performed by experienced surgeons can be applied effectively and safely, with shorter operative times and lower complication rates. Full article