Fibroblast growth factor receptor 2 (FGFR2) alterations have emerged as an important targetable oncogenic driver in a biologically distinct subset of biliary tract cancers (BTCs), particularly intrahepatic cholangiocarcinoma (iCCA), alongside other actionable genomic events such as IDH1 mutations, BRAF V600E, HER2 amplification and MSI-H. FGFR2 fusions and mutations define a distinct molecular subgroup whose prevalence varies across geographic regions and etiologic backgrounds such as liver fluke-associated disease. Clinical studies of both reversible and irreversible FGFR inhibitors have demonstrated meaningful activity in FGFR2-rearranged iCCA, while also highlighting a characteristic toxicity profile dominated by on-target hyperphosphataemia. Parallel translational work using cfDNA-based liquid biopsy has mapped a spectrum of secondary kinase-domain mutations that underlie acquired resistance, informing the development of next-generation FGFR2-selective inhibitors (eg, lirafugratinib) and combination strategies with EGFR/ERBB blockade. Collectively, these data underscore the need for comprehensive molecular profiling and innovative umbrella trial designs to optimise targeted therapy in this rare, biologically heterogeneous malignancy.

Introduction: Rescue stenting (RS) is a recognized bailout strategy following failed endovascular thrombectomy (EVT) for acute ischemic stroke (AIS). First-line stenting (FLS) has emerged as a potential alternative to avoid vascular injury and improve outcomes. However, direct comparisons between these strategies remain limited. Methods: We conducted a comparative analysis of FLS and RS using data from the RESISTANT registry, an international, multicenter, retrospective cohort of AIS patients who received intracranial stenting during EVT from 2016 to 2023. Patients were categorized by stenting strategy: FLS (stent placed without prior thrombectomy) or RS (stent placed after failed thrombectomy). The primary effectiveness outcome was functional independence (modified Rankin Scale [mRS] 0–2) at 90 days. The primary safety outcome was symptomatic intracranial hemorrhage (sICH). Propensity score inverse probability of treatment weighting (IPTW) was used to adjust for baseline differences. Results: Among 827 patients, 723 were in the RS cohort and 104 in the FLS cohort. Compared to RS, FLS patients more often had diabetes (46.2% vs. 35.2%, p =0.03), prior stroke (46.2% vs. 25.3%, p <0.001), prior antiplatelet use (50.0% vs. 27.7%, p <0.001), and known ICAS (28.8% vs. 6.0%, p <0.001). They also had lower baseline NIHSS scores at presentation (median 8 vs. 14, p <0.001) and shorter onset-to-recanalization times (median 363 vs. 392 min, p =0.006). After IPTW adjustment, functional independence was similar between groups (OR=0.64; 95% CI 0.38–1.07), as was the risk of sICH (OR=0.93; 95% CI 0.34–2.59). No significant differences were observed in secondary outcomes including successful reperfusion, mortality, or procedural complications. Outcomes were similar in both the anterior circulation subgrou (n=589; functional independence: OR=0.62; 95% CI 0.60–1.25; sICH: OR=0.81; 95% CI 0.30–2.18) and the posterior circulation subgroup (n=234; functional independence: OR=0.82; 95% CI 0.32–2.10; sICH: OR=0.81; 95% CI 0.30–2.18). Conclusion: FLS and RS strategies during EVT for AIS demonstrated comparable safety and efficacy. Prospective, randomized trials are needed to better define optimal treatment approaches.

Introduction: Intracranial stenting during endovascular thrombectomy (EVT) is a common practice in the setting of failed reperfusion or severe stenosis. Immediate stent patency requires periprocedural antiplatelet therapy (APT). How APT intensity interacts with prior intravenous thrombolysis (IVT) to influence hemorrhagic risk remains uncertain. We aimed to assess whether the APT regimen modifies the association of IVT with early intracranial hemorrhage after intracranial stenting during EVT. Methods: This was a subanalysis of the RESISTANT registry, a multicenter, international, retrospective cohort (2016 to 2023) of adults with acute ischemic stroke who underwent intracranial stenting during EVT. APT regimens were categorized as conservative (intravenous or oral aspirin alone, or aspirin plus an oral P2Y12 inhibitor) and aggressive (any regimen including intravenous GPIIb/IIIa inhibitor or intravenous cangrelor). Four main groups were compared according to the APT regimen (conservative/aggressive) and the use of IVT (+/-). The primary outcome was a composite of sICH and parenchymal hematoma types 1 and 2 (sICH-PH2-PH1). Multivariable logistic regression models were used to evaluate the interaction between IVT and APT, adjusting for clinically relevant covariates. Results: Among the 823 included patients, 44 (5.3%) received conservative APT with IVT, 130 (15.8%) received conservative APT without IVT, 145 (17.6%) received aggressive APT with IVT, and 504 (61.2%) received aggressive APT without IVT. Among patients who received IVT, sICH-PH2-PH1 rates were 9.3% with conservative APT and 10.7% with aggressive APT; among those without IVT, rates were 3.2% and 9.9%, respectively. Administration of IVT (adjusted odds ratio [aOR] 5.84, 95%CI 1.07 to 43.92; p=0.05) and aggressive APT (aOR 4.81, 95% CI 1.41 to 30.22; p=0.03) were each associated with higher odds of hemorrhagic complications, with a significant IVT by APT interaction (P interaction =0.05; Figures 1 and 2 ). Within the aggressive APT plus IVT subgroup, sICH-PH2-PH1 occurred in 20% of patients treated with cangrelor and 6.1% treated with a glycoprotein IIb/IIIa inhibitor ( Figure 3 ). Conclusion: Among patients requiring intracranial stenting, aggressive periprocedural APT and prior IVT are each associated with higher hemorrhagic risk, with the combination showing the worst observed crude outcome. Prospective evaluation of protocolized APT pathways in the IVT setting is warranted.

Immigrant populations frequently encounter barriers when accessing healthcare services, potentially affecting patient safety, healthcare utilization, and clinical outcomes. Understanding these barriers is essential for improving equitable and patient-centered care. A systematic review of qualitative and quantitative studies was conducted in accordance with PRISMA 2020 guidelines. PubMed/MedLINE, Embase, Cochrane Library, PsycINFO, EconLit, Web of Science (WoS), and CINAHL were searched from January 2005 to August 2023. Inductive thematic analysis was used to synthesize findings across studies. The review was not prospectively registered, included only English-language studies, and relied predominantly on qualitative evidence. Heterogeneity across study designs and healthcare settings may limit generalizability. The authors received no external funding for this study. Three interconnected themes consistently emerged: limited transcultural competence, language barriers, and discrimination in healthcare. Inadequate cultural competence was associated with communication difficulties and reduced care effectiveness. Language barriers contributed to miscommunication, delayed care, and increased healthcare utilization. Experiences of discrimination were linked to reduced trust in healthcare systems and poorer patient engagement. These factors negatively influenced patient safety, satisfaction, and clinical outcomes. Immigrant patients face persistent and interrelated barriers to healthcare access. Strengthening culturally responsive care, improving access to professional interpreter services, and addressing discriminatory practices are essential to improving patient safety, satisfaction, and clinical outcomes. Future research should evaluate targeted interventions aimed at improving communication, cultural competence, and healthcare equity.

BACKGROUND Older women face disproportionate health challenges, exacerbated by multiple unprecedented challenges such as global aging, disease outbreaks, and geopolitical as well as technological upheavals. This study examines technology-based mental health interventions for this demographic, aiming to inform policy. METHODS A systematic review of randomized controlled trials (RCTs) targeting older women's mental health post-COVID-19 was conducted using databases like Web of Science and PubMed, adhering to PRISMA guidelines and registered with PROSPERO (CRD42020194003). RESULTS A total of 3463 articles were screened for eligibility, among which, 17 RCTs met the inclusion criteria. The review results show that 17 RCTs were conducted in middle-income and high-income countries. Fifteen RCTs generated statistically significant outcomes and reported specific aspects of their interventions to improve the mental health of older women. CONCLUSION Technology-based interventions show promise for improving older women's mental health. Policy recommendations include establishing comprehensive mental health centers, implementing universal healthcare, promoting digital literacy, and strengthening public awareness campaigns.

Health literacy (HL) and physical literacy (PL) are hypothesized to be important determinants of physical activity (PA) in older individuals. The aim of the study was to evidence possible associations between PL, HL, and PA, evidencing structural comparison of exercising and nonexercising postmenopausal women. The sample included 62 females (+60 years of age) divided into exercising (E; n=37) and nonexercising groups (NE; n=25). Participants were tested on HL (via the European Health Literacy Survey Questionnaire), PL (via the Perceived Physical Literacy Questionnaire), and PA (via the Nordic Physical Activity Questionnaire – short) in controlled settings. Group-specific Pearson’s correlation matrices were calculated to examine associations among PL, HL, and PA. Between-group differences in correlations were tested using Fisher’s z-transformation with false discovery rate correction, and structural patterns were further explored using correlation network analysis. Fisher’s z tests identified significant between-group differences in selected associations, with E women showing a stronger bridging role of PL and weaker cognitive constraints on PA. Network analyses further demonstrated greater connectivity and cognitive dominance in NE women, whereas E women exhibited more differen- tiated and functionally organized relational structures. The results suggest that PA-related interventions targeting older women should move beyond information provision and explicitly promote PL development.

In this study, a model was developed to calculate the power required for the circumferential cutting of solid wood in the longitudinal direction, considering the relevant technological parameters and mechanical properties of the wood. Based on measurements of different combinations and using the Response surface method (RSM) and Central composite design (CCD), a model was created that, in its derived version, considers the cutting width and depth, the diameter and speed of the tool, the number of cutting edges and sharpness of the cutting edge, the feed rate of the workpiece, and the density and moisture content of the wood. The model can be used to calculate the cutting power of various tree species with densities ranging from 400 to 700 kg/m3, moisture contents from 8 to 16%, and a wide range of cutting-edge sharpness, from a sharp cutting edge with a tip radius of 5 µm to a blunt cutting edge with a tip radius of 35 µm. The model is designed for a rake angle of 20°, the value most frequently used in practise. ANOVA analysis was used to determine the suitability of the model, which is highly significant with an R2 value of 0.93 and an average deviation of the calculated values from the measured values of 8.8%. The model is robust and therefore useful in the wood industry for predicting energy consumption in the processing of solid wood.

Objective: The objective of this study is to compare the analgesic effects of functional magnetic stimulation (FMS) and interferential current therapy (IFC) in patients with knee osteoarthritis (KOA) before and after treatment. Methods: This prospective pilot study included 30 patients with KOA, who were randomly assigned to two groups: FMS (n = 15) and IFC (n = 15). Both groups received 20 treatment sessions over four weeks. Pain intensity was assessed using the visual analog scale (VAS) pre- and post-treatment. Non-parametric statistical tests were applied due to the small sample size and non-normal distribution of the data. Results: In the FMS group, the median VAS score decreased significantly from pre-intervention (Me = 7.0; IQR, 5.0-7.0) to post-intervention (Me = 2.0; IQR, 1.0-2.0), with z = −3.43, p < 0.001. In the IFC group, there was also a significant decrease in the median VAS score from pre-intervention (Me = 7.0; IQR, 5.5-8.0) to post-intervention (Me = 5.0; IQR, 4.0-6.0), z = −3.47, p < 0.001. The Mann-Whitney U test demonstrated a statistically significant difference; the median ΔVAS was significantly higher in the FMS group (Me = 4; IQR, 3.5-6.0) than in the IFC group (Me = 2; IQR, 1.0-2.0) (U = 45, Z = −4.576, p < 0.001). Conclusion: FMS may be a more effective non-invasive treatment option for pain reduction in patients with KOA compared with IFC.

BACKGROUND Minimally invasive surgery is rapidly expanding globally, yet there is insufficient knowledge of how to scale this technology safely and equitably across diverse health systems. We aimed to identify health-system factors associated with safe implementation of minimally invasive surgery globally, using minimally invasive cholecystectomy as a tracer procedure. METHODS We conducted a multicentre, prospective cohort study of consecutive adults undergoing cholecystectomy between July 31 and Nov 19, 2023, in 1218 hospitals across 109 countries. Data were collected by more than 10 000 health-care workers using a core measurement set mapped to the WHO Health System Building Blocks and the Global Patient Safety Action Plan. The primary outcome was 30-day procedure-specific complications, with multilevel logistic regression used to examine associations between health-system features and patient outcomes. This study is registered on ClinicalTrials.gov (NCT06223061). FINDINGS Among 52 187 included patients, the adjusted procedure-specific complication rate varied 40-fold between hospitals, from 0·3% in the lowest risk quintile to 12·1% in the highest risk quintile. Despite large structural differences across income groups in access to minimally invasive surgery, diagnostics, and emergency services, country income level was not independently associated with complication rates (adjusted odds ratio [OR] 0·81 [95% CI 0·59-1·10] for upper-middle income vs high income and 0·99 [0·70-1·39] for lower-middle income or low income vs high income). Three modifiable hospital-level factors were strongly associated with safer outcomes: establishment of local simulation-based training facilities (adjusted OR 0·78 [0·71-0·86]; p<0·0001), adoption of intraoperative safety and communication strategies (0·87 [0·79-0·96]; p=0·0046), and on-site CT diagnostics (0·79 [0·65-0·97]; p=0·0220). Training facilities showed the greatest benefit in hospitals with limited infrastructure and an inexperienced workforce: the number needed to treat to prevent a procedure-specific complication was 21 (95% CI 14-35; p<0·0001). INTERPRETATION Safe implementation of minimally invasive surgery varies widely worldwide but is not defined by national income level; differences in outcomes reflect the ability of health systems to adopt and safely deploy new surgical techniques. We identified for the first time that the presence of local simulation-based training facilities is independently associated with improved patient outcomes. Simulation appears to be fundamental to the safe delivery of minimally invasive surgery, particularly in resource-constrained settings. Together with safety systems and diagnostic capacity, these findings offer actionable targets for health systems seeking to equitably scale up essential surgical technologies. FUNDING NIHR Global Health Research Unit and Wellcome Leap SAVE Programme.

This study aims to examine how the design of the work environment and its key dimensions—job design, employee involvement in goal setting and decision-making, as well as teamwork practices and open communication—affect productivity, organizational identification, and workforce stability in organizations in Bosnia and Herzegovina. Using a quantitative research approach and linear regression analysis on a sample of employees from the industrial sector, the results indicate that the work environment exerts a statistically significant and consistent effect on all observed outcomes. Among the analyzed components, employee involvement in decision-making proved to be the most significant factor, indicating that a sense of appreciation and the ability to influence one's own work have a strong effect on employees' motivation, loyalty, and willingness to stay in the organization. The results show that the impact of work environment design on employee performance is largely realized through strengthening employees’ connection to the organization. When the work environment is designed to ensure pleasant working conditions in which employees are actively involved in work processes, it becomes a powerful source of employee motivation and engagement. Therefore, a policy of adequately designing the work environment does not represent merely a short-term solution, but rather a realistic and sustainable approach to strengthening organizational stability and long-term success.