Search Results (5,053)

This review summarises current evidence on renal cell carcinoma (RCC) with sarcomatoid dedifferentiation (sRCC), with an emphasis on diagnosis, prognostic stratification, and treatment. Sarcomatoid dedifferentiation is characterised by high-grade spindle cell morphology, occurs in 2–26% of all RCC patients, predominantly in the clear cell subtype (~70%), and is WHO/ISUP grade 4 regardless of extent of involvement. Thus, sRCC represents a pathological transformation rather than a distinct entity. Diagnosis requires biopsy or nephrectomy; immunohistochemical (IHC) retention of PAX8, cytokeratins, and vimentin alongside loss of subtype-specific markers distinguishes sRCC from primary renal sarcoma. On CT, sRCC typically presents as a large, heterogeneous mass with extensive necrosis; 18F-FDG PET/CT carries independent prognostic value, though no feature is pathognomonic. Sarcomatoid features are approximately five times more prevalent in patients with metastatic vs. localised disease (~20 vs. ~4%), and their identification should prompt risk stratification. Median overall survival (OS) in metastatic sRCC is 5.9–13.3 months, though recent data suggest improvement with novel therapies. Sarcomatoid dedifferentiation is characterised by enrichment of alterations in TP53, BAP1, CDKN2A/B, and NF2 on a background of founder RCC mutations, generating an immune-inflamed tumour microenvironment with elevated CD8+ T cell infiltration and PD-L1 expression that may underpin the heightened sensitivity of sRCC to immune checkpoint inhibitors (ICI). Surgery remains the cornerstone in localised disease, although recurrence rates approach 80% within two years. Adjuvant pembrolizumab significantly improved disease-free survival in high-risk localised RCC with sarcomatoid features (KEYNOTE-564; NCT03142334). In the metastatic setting, nivolumab plus ipilimumab and pembrolizumab plus axitinib are preferred first-line regimens. Full article

This study examines whether China’s Intelligent Manufacturing Pilot Demonstration Program is associated with changes in Huazheng-rated environmental, social, and governance (ESG) performance among listed manufacturing firms. Using a panel of 2581 firms from 2012 to 2022, we exploit the staggered admission of 91 pilot firms. The preferred doubly robust group-time difference-in-differences estimator yields an average treatment effect of 0.881 Huazheng points, positive at the 10% level. The conventional firm and year fixed-effects estimate is 1.801 points and significant at the 1% level; it is retained as a benchmark rather than the main policy estimate. The direction remains positive across alternative fixed effects, lagged controls, a pre-COVID-19 sample, reweighting, matching, stacked estimation, randomization inference, wild-cluster bootstrap inference, and leave-one-out tests. Under the benchmark specification, the environmental and governance ratings rise significantly, whereas the social estimate is imprecise. The organizational regressions are consistent with possible information verification, managerial incentive, and financing channels, and cross-fitted double machine learning provides a functional-form check. Overall, pilot designation is associated with higher Huazheng-rated ESG performance, with evidence consistent with a possible policy effect. Selective designation and the provider-specific outcome preclude stronger claims about independently verified corporate sustainability. Full article

Background/Objectives: Real-world antidepressant use for depressive disorder varies across clinical settings. This study aimed to characterize prescribing pathways and evaluate the comparative safety of frequently prescribed antidepressants in a large multicenter cohort with newly diagnosed depressive disorder. Methods: We conducted a retrospective multicenter observational study using electronic health record data standardized to the OMOP Common Data Model (1999–2026) in adults initiating antidepressants. Prescribing patterns among 13,381 patients were visualized using sunburst plots and Sankey diagrams. Comparative safety, escitalopram vs. sertraline and trazodone, was evaluated across 18 hospitals (n = 44,542) for nine clinical safety outcomes using propensity score-matched Cox proportional hazards models and empirically calibrated random-effects meta-analysis. Results: Selective serotonin reuptake inhibitors, particularly escitalopram (21.4%, n = 2868), were the preferred antidepressant. Common adjunctive medications included trazodone (14.6%, n = 794) and quetiapine (14.0%, n = 761), though utilization varied across hospitals. No clear differences were detected for most safety outcomes between cohorts. However, empirically calibrated QTc prolongation risk was significantly increased with sertraline relative to escitalopram (HR 1.75, 95% CI 1.10–2.78), a signal requiring further confirmation. Conclusions: This study demonstrates substantial institutional variation exists in real-world antidepressant treatment pathways and combination strategies. While comparative safety profiles were broadly comparable across evaluated outcomes, the isolated QTc prolongation signal for sertraline warrants targeted external confirmation. Furthermore, trazodone and escitalopram cohorts should not be regarded as clinically interchangeable first-line options, supporting individualized, evidence-based antidepressant selection in routine clinical practice. Full article

Background: People who inject drugs (PWID) comprise the majority of patients with native tricuspid valve (TV) infective endocarditis (IE). Many patients require surgical repair or replacement of their TV, but some may be deemed ineligible for surgical management due to high operative risk or patient preference. Vacuum-assisted percutaneous mechanical aspiration (PMA) has emerged as a potential alternative to surgical management in this population. The objective of this study was to describe real-world patient characteristics and clinical outcomes in PWID who underwent PMA or surgical management of TV IE. Methods: We retrospectively reviewed PWID hospitalized with endocarditis at a single tertiary care center (2016–2025) who underwent an isolated PMA or surgical TV repair/replacement (TVR). Baseline demographic, clinical, microbiologic, and echocardiographic characteristics were described. Clinical outcomes were compared descriptively between groups, recognizing imbalances in treatment selection. Results: A total of 40 PWID met inclusion criteria; 17 underwent PMA and 23 underwent surgical TVR. There was substantial baseline clinical heterogeneity between the two groups. Procedural success was numerically higher with surgery than with PMA (95.7% vs. 88.2%). Clinical success, a composite of procedural success, treatment completion, and lack of need for reintervention, was numerically higher in the TVR group (73.9% vs. 52.9%). One-year mortality was similar between groups. Conclusions: In this single-center retrospective observational cohort of PWID with isolated TV IE, there was no statistical difference in composite clinical or procedural success between patients who underwent PMA or TVR. PMA may be a feasible source-control strategy for select patients not eligible for immediate surgery; however, larger prospective studies are needed to define optimal patient selection factors and comparative effectiveness. Full article

Atrial fibrillation (AF) and heart failure (HF) frequently coexist, but the clinical relevance of AF may differ according to whether it appears to be a potentially reversible contributor, an aggravating factor in established HF, or a marker of advanced substrate. The driver–modifier–marker lens used in this review is a provisional, nonvalidated aid to clinical reasoning and should not be interpreted as a treatment score. This narrative review was informed by dated searches of PubMed/MEDLINE, the Cochrane Library, and OpenAlex through 29 July 2026, followed by a targeted update on 30 July 2026. It considers HF with reduced, mildly reduced, and preserved ejection fraction together with AF timing, burden, ventricular-rate exposure, myocardial substrate, and reversibility. Early rhythm control may be particularly relevant when AF is recent or temporally associated with ventricular dysfunction, symptoms, decompensation, or inadequate cardiac resynchronization therapy delivery. Evidence supporting catheter ablation is most direct in suspected AF-mediated cardiomyopathy and selected HFrEF populations, whereas evidence in HFpEF more consistently supports symptom relief, improved exercise hemodynamics, and AF-burden reduction than mortality reduction. Pulmonary vein isolation remains the procedural foundation. Radiofrequency, cryoballoon, and pulsed-field ablation are effective in broad AF populations, but HF phenotype-specific prognostic superiority has not been established for any energy source. Clinical decisions should reflect the design and directness of the evidence together with expected benefit, rhythm durability, procedural risk, patient-reported outcomes, stroke prevention, guideline-directed HF therapy, risk-factor management, and patient preference. Full article

Background/Objectives: Anticoagulation in advanced chronic kidney disease (CKD) remains challenging due to limited representation in clinical trials, resulting in uncertainty regarding optimal drug selection, dosing, and monitoring strategies. Methods: We conducted a cross-sectional, web-based survey of clinicians involved in CKD care and anticoagulation prescribing. The questionnaire explored respondent characteristics, methods of renal function estimation, anticoagulant selection across common CKD scenarios, anticoagulants’ dosing and monitoring practices, and approaches to anticoagulation in nephrotic syndrome. Results: Fifty-seven clinicians participated in the survey. Unfractionated heparin was the preferred agent for venous thromboembolism (VTE) prophylaxis in patients with stage 4 and 5 CKD, or on dialysis. For acute VTE treatment, anticoagulant choice varied by CKD severity, with unfractionated heparin, direct oral anticoagulants (DOACs), and low-molecular-weight heparin (LMWH) all reported to be used depending on stages of CKD. Warfarin and DOACs were commonly used for treatment of chronic VTE and atrial fibrillation (AF), with warfarin more frequently selected in patients receiving dialysis. Apixaban was the most frequently reported DOAC, typically at a dose of 2.5 mg twice daily in advanced CKD and dialysis. Renal function estimation methods varied, with Cockcroft–Gault most used overall, while nephrologists more frequently reported MDRD or CKD-EPI equations. Most respondents reported not routinely monitoring DOAC levels, and the majority indicated the absence of a structured multidisciplinary team (MDT) for managing anticoagulated CKD patients. Clinical practice varied according to specialty, experience, and healthcare setting, particularly in anticoagulant selection, dosing strategies, and use of risk stratification tools. Conclusions: Anticoagulation practices in advanced CKD are highly heterogeneous, reflecting persistent evidence gaps. While unfractionated heparin and warfarin remain central in patients with stage 5 CKD or on dialysis, DOAC use—particularly apixaban—has expanded, often with empiric dose reduction. These findings underscore the need for clearer guidance, standardized approaches to renal function assessment, multidisciplinary care pathways, and prospective studies focusing on anticoagulation use in CKD populations. Full article

Managing the transition risks of carbon-intensive firms is essential for reconciling climate governance with the stable operation of the real economy; nevertheless, existing scholarship has yet to fully elucidate how climate policy uncertainty contributes to the formation of these risks. In this paper, we develop a firm-specific measure of climate policy uncertainty exposure by integrating China’s aggregate climate policy uncertainty index with climate-risk-related textual data retrieved from listed companies’ annual reports. Drawing on a panel dataset of A-share listed companies in nine carbon-intensive sectors over 2010–2023, we employ a partial-linear double/debiased machine-learning methodology to investigate how climate policy uncertainty exposure influences multidimensional firm transition risk. Our baseline estimations indicate that greater climate policy uncertainty exposure is associated with a statistically significant rise in transition risk among high-carbon firms, with the preferred model producing a coefficient estimate of 0.0243. These findings remain robust to an array of sensitivity checks and endogeneity-correction procedures. Mechanism analysis provides evidence consistent with four potential channels involving weaker intra-industry competition, lower corporate risk-taking, tighter financing constraints, and higher agency costs. Heterogeneity examinations reveal that the detrimental impact is particularly evident among larger enterprises, high-technology companies, and firms characterized by comparatively lower pollution levels. Further analysis based on conditional average treatment effects and best linear predictors reveals that media supervision and the presence of long-term institutional investors substantially reduce the extent to which climate policy uncertainty translates into firm transition risk. This study provides firm-level empirical evidence elucidating how climate policy uncertainty shapes multidimensional transition risk in the low-carbon transformation of high-carbon industries. Full article

The rapid expansion of fiber-reinforced polymers (FRPs) in wind energy, transportation, and aerospace is generating increasing amounts of accompanied waste, making effective valorization essential to a circular economy. This review compares FRP recovery technologies in terms of recovered-fiber quality, operating conditions, post-treatment, environmental impacts, and industrial applicability. Then, it also examines direct reuse, FRP remanufacturing, and reuse in cementitious composites. Quantitative synthesis indicates that high-quality recycled carbon fibers (rCFs) generally retain more than 90% of their original strength, whereas mechanically recovered glass fibers (rGFs) typically retain approximately 70–90%. The preferred pathway depends on the intrinsic value, damage state, morphology, and residual properties. Components with sufficient residual capacity should be directly reused; high-quality fibers are better suited to polymer remanufacturing; and heterogeneous or lower-grade glass-FRP (GFRP) fractions are more compatible with cementitious applications, where mechanically recycled GFRP can provide interfacial bond strengths comparable to conventional engineering macrofibers. Future research should establish quantitative links among recovered material quality, processing, interfacial behavior, and end-use performance, while adopting consistent environmental and economic assessment boundaries. A graded utilization framework is therefore required to support both large-scale and value-added reuse of FRP waste. Full article

China’s pursuit of its dual-carbon targets amid rapid artificial intelligence (AI) development raises an important question: do the environmental implications of AI innovation change as regional innovation advances? Using a balanced panel of 30 Chinese provinces from 2011 to 2024, this study measured patent-based AI innovation intensity using applications identified through a strict AI patent classification. Linear and quadratic models with province and year fixed effects were estimated, and the Lind–Mehlum test was used to assess the shape of the relationship within the observed range. The preferred specification indicates an inverted-U-shaped association: carbon emission intensity initially increases with patent-based AI innovation but declines beyond an interior turning point. The negative quadratic coefficient remains stable when the emissions data source, patent classification, sample period, treatment of outliers, and timing of the AI terms are varied. Supplementary Bartik and copula-control analyses preserve the negative curvature, although their identification limitations preclude a definitive causal interpretation. A Kaya-based exact decomposition shows that the estimated curvature is concentrated in energy intensity rather than the carbonization factor. Human capital strengthens the estimated concavity, while the clearest regional contrast is observed between central and eastern China, with the strongest curvature in the central provinces. These findings suggest that greater AI patenting does not automatically reduce emissions. Its environmental implications depend on the stage of regional innovation and its interaction with energy efficiency and absorptive capacity. Policies promoting AI innovation should therefore be coordinated with cleaner energy supply, efficiency improvements, and human capital investment. More broadly, the study provides a stage-sensitive basis for evaluating the sustainability implications of patent-based AI innovation through measurable changes in carbon emission intensity. Full article

Objectives: To determine whether the superior anatomical control achieved with a treat-and-extend (T&E) anti-VEGF regimen translates into better five-year visual outcomes than a pro re nata (PRN) regimen in treatment-naïve center-involving diabetic macular edema (CI-DME), and to characterize the anatomical–functional relationship. Methods: In this retrospective propensity-score–matched survivor cohort, one eye per patient was analyzed. One-to-one nearest-neighbor matching balanced 14 baseline covariates. Longitudinal best-corrected visual acuity (BCVA) and central subfield thickness (CST) were analyzed using linear mixed-effects models with matched-pair clustering. Absence of a clinically meaningful visual difference was evaluated using two one-sided tests (TOST) with a prespecified ±5-letter equivalence margin. The anatomical–functional relationship was assessed by segmented regression. Sensitivity analyses included inverse probability of treatment weighting, doubly robust estimation, inverse probability of censoring weighting, best-/worst-case imputation, interval-censored recurrence modeling, and E-value analysis. Results: Both regimens improved BCVA, with no clinically meaningful difference at five years (T&E +6.2 ± 14.6 vs. PRN +6.9 ± 14.0 letters; difference −0.7 letters; 90% CI, −2.4 to 1.0; TOST p < 0.001). T&E achieved greater CST reduction (−172.3 vs. −114.2 µm; difference −58.1 µm; p < 0.001), higher dry-macula rates (73.8% vs. 59.5%; p < 0.001), fewer recurrences (2.2 vs. 3.9; p < 0.001), and fewer monitoring-only visits (14.6 vs. 28.4; p < 0.001), but required 53% more injections (25.1 vs. 16.4; p < 0.001). Segmented regression identified a breakpoint at 148 µm CST reduction; additional thinning beyond this threshold was not associated with further visual improvement. Baseline BCVA, ellipsoid zone disruption, and diabetic retinopathy severity, but not treatment regimen, independently predicted five-year vision. Results were consistent across sensitivity analyses. Conclusions: Among patients completing five years of therapy, additional anatomical drying beyond an exploratory, cohort-specific breakpoint of approximately 150 µm CST reduction was not associated with further measurable visual gain in this observational cohort. Regimen selection should therefore reflect treatment burden, monitoring requirements, and patient preference rather than anticipated visual superiority. Because the cohort included only patients completing five years of follow-up, these findings apply to adherent patients and should not be generalized to unselected populations. Full article

Background: Biological treatment of psoriasis has revolutionized the therapy of this disease, in most cases enabling complete remission of skin lesions. Methods: This study aimed to analyze real-world evidence from 165 patients (mean age 38.1 ± 5.66) treated with 11 biological drugs at our Dermatology Department. Results: Skin lesion severity, expressed by Psoriasis Area and Severity Index (PASI) and Body Surface Area (BSA), improved significantly throughout the treatment, along with the quality of life, expressed by Dermatology Life Quality Index (DLQI) (all p < 0.0001). We observed a statistically significantly higher reduction in skin lesion severity and life quality improvement with IL-23 and IL-17 inhibitors compared to TNFα inhibitors (both p < 0.0001). Secondary loss of response was observed in 26.7% of patients treated with anti-TNF agents, compared to 15.0% in the anti-IL-23 group and 8.3% in the anti-IL-17 group (χ² test, p = 0.0683). Patients who had been treated in the past with biologics had significantly higher PASI and BSA at week 16 of therapy compared to those who were bio-naïve. A positive correlation was demonstrated between PASI at 16 weeks and BMI (R = 0.15; p = 0.0396). There was no correlation between the duration of psoriasis, sex, or age of patients when introducing biologics and PASI at any of the timepoints (p > 0.05). The most frequent side effects were infections, occurring mainly in patients on anti-TNFα agents and bimekizumab. Conclusions: IL-17 and IL-23 inhibitors demonstrated superior efficacy compared to TNFα inhibitors, with higher rates of complete skin clearance and a lower tendency toward loss of response. The worst efficacy and the highest rate of loss of response were observed in case of adalimumab. These findings support the increasing role of IL-17 and IL-23 inhibitors as preferred therapeutic options in psoriasis. Previous biologic exposure and higher BMI seem to be associated with poorer therapeutic outcomes. Overall, biological treatment is an effective, rapid, and safe therapeutic option. Full article

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for pain, inflammation, and fever. Although many NSAIDs are available without a prescription, inappropriate use may increase the risk of renal, gastrointestinal, and cardiovascular complications. This study evaluated NSAID dispensing patterns and potential risk practices in community pharmacies in the Eastern Province of Saudi Arabia. Methods: A cross-sectional study was conducted in 90 community pharmacies across Al-Ahsa, Al-Dammam, and Jubail Industrial City between February and March 2025. Data on demographics, NSAID type, indication, dosage, frequency, duration, and concomitant medication use were collected and analyzed descriptively. Results: Among the 171 documented NSAID dispensing cases, 98 (57.3%) occurred without a prescription, whereas 73 (42.7%) involved prescription-based dispensing. Ibuprofen (62%) and diclofenac (36.3%) were the most commonly dispensed agents, with oral tablets being the preferred formulation (76.6%). Most documented treatment durations were short (3–7 days) with once- or twice-daily dosing. Common documented indications included dental conditions, pain, and inflammation, although the indication was not specified in 57.3% of cases. At least one potential interaction was identified in 11(7.8%, 95% CI 4.4–13.4%) of the 141 cases with concomitant medication use, corresponding to 13 (5.9%, 95% CI 3.5–9.9%) potential interaction pairs. Conclusions: Frequent non-prescription NSAID dispensing, incomplete documentation, and potentially clinically relevant drug interactions highlight the need to strengthen medication review, documentation, public awareness, regulatory oversight, and pharmacist counseling in community pharmacy practice. Full article

This study developed a composite rejuvenator comprising recycled polyethylene wax (PREW), waste cooking oil (WCO), and epoxidized soybean oil (ESO) activated by the tertiary amine catalyst BDMA to improve the intermediate-temperature rejuvenation of aged SBS-modified asphalt binder. The binder was subjected to combined rolling thin-film oven and pressure aging vessel aging. Conventional tests, rotational viscosity, bending beam rheometer, multiple stress creep recovery, fluorescence microscopy, and Fourier transform infrared spectroscopy were used to evaluate macroscopic, rheological, and microstructural properties. Aging hardened and embrittled the binder, increased softening point and viscosity, reduced penetration and ductility, and disrupted the polymer-rich phase. PREW reduced flow resistance and retained relatively high-temperature structural stability, whereas WCO improved flexibility and flowability, although excessive softening impaired high-temperature stability. ESO/BDMA treatment was accompanied by changes in oxygen-containing functional group-related absorption regions and improved apparent connectivity of the SBS-rich phase. Among the tested temperatures, 120 °C provided the best overall balance among the evaluated properties, satisfying low-temperature stress-relaxation requirements while limiting high-temperature creep deformation. These results identify 120 °C as the preferred treatment temperature for the PREW/WCO/ESO-BDMA rejuvenation system. Full article

Background: The rabbit (Oryctolagus cuniculus) is a currently indispensable pre-clinical model for fundamental discovery and translational research in glaucoma surgery. While not fully representative of the human eye, the rabbit often serves as the site of the first robust assessment of a new chemical entity in an anatomically and physiologically relevant setting. In later stages of development, the rabbit is also a critical model for regulatory-facing Good Laboratory Practice (GLP)-graded pre-clinical safety studies. However, while guidelines exist for human glaucoma surgeries in terms of patient profile vs. surgery type and success criteria, there is limited collated information available on how rabbit glaucoma filtration surgeries are designed, use and mode of administration of anti-metabolite Mitomycin-C (MMC) and post-operative antibiotic and anti-inflammatory dosing regimes. These disparities limit cross-comparability in studies and encourage sub-optimal study design and incomplete reporting. Methods: This review investigated and collated current procedural and reporting practices based on 100 peer-reviewed rabbit glaucoma filtration surgery publications from the years 2011–2025. Publications meeting acceptance criteria were segmented into pre-operative designs (ethical approval, rabbit characteristics, study duration), intra-operative (surgery type, surgical approach, use of MMC) and post-operative follow-up (antibiotics, anti-inflammatories, analysis and adverse events). Results: It was found that there were clear preferences in animal model selection, study design and intra-/post-operative anti-fibrotic/inflammatory treatment regimes. Additionally, there were several areas identified where reporting was ambiguous or omitted, e.g., rabbit age, post-operative treatments, adverse events. The levels of omission were 16–30% and represent areas for improvement and highlight the need for ongoing review in pre-clinical research. Full article

Pulsed Electric Fields (PEF) offer significant potential to enhance energy efficiency and reduce reliance on SO₂ and other chemical preservatives, aligning with current sustainability and health demands. This work evaluates PEF industrial viability for wine stabilisation through a multidisciplinary pilot-scale approach (108 L/h). A sulfur-free comparative trial evaluated four sequential bipolar PEF treatments (20–23 kV/cm; 19–34 kJ/kg) against stabilisation with a commercial chitosan–glucan complex. PEF caused significant effects on microbial kinetics: B. bruxellensis was successfully maintained below the detection limit and lactic acid bacteria (LAB) were undetected by the end of the trial. Standard oenological parameters showed no relevant changes, except for lactic acid dynamics, corroborating LAB knockdown. Regarding metal ion migration into the food matrix, Fe, Ni, and Cr were assessed. No significant variations were found for Fe and Ni compared to the control group; all elements presented residual concentrations compatible with international regulatory guidelines. Sensory analysis revealed that PEF-treated wines exhibited lower perceived bitterness and higher colour intensity, driven by B. bruxellensis proliferation in control wines. In total, 75% of panellists preferred PEF wines. OPEX analysis demonstrates industrial competitiveness for medium-to-large scale, reducing consumable costs over 10-fold (0.6064 vs. 6.50 €/hL), excluding initial CAPEX. These findings validate multi-stage, pilot-scale PEF as a competitive and electrochemically safe technology to transition toward sustainable reduced-SO₂ or SO₂-free winemaking. Full article