There is a lack of robust evidence regarding immunosuppressive therapy in children and adolescents after kidney transplantation (KTx), and as such, international practice is highly variable. Recent clinical practice recommendations advocating individualized immunosuppressive strategies that incorporate newer agents are often not implemented. This can potentially contribute to reduced patient and renal allograft survival. The guideline was developed between January 1, 2024, and December 12, 2025, according to the Guidance Manual of the German Association of Scientific Medical Societies by the German Societies for Pediatric Nephrology, Nephrology, Transplantation, and Pediatrics, the German Kidney Association, the International Pediatric Transplant Association, the European Society for Pediatric Nephrology and the Members of the Cooperative European Pediatric Renal Transplant Initiative. This evidence- and consensus-based guideline provides up-to-date, state-of-the-art recommendations for immunosuppressive therapy after KTx in pediatric kidney transplant recipients. It is based on the best available evidence and the consensus of the relevant German Medical Societies, Members of the Cooperative European Paediatric Renal Transplant Initiative, and the working group on transplantation of the European Society for Paediatric Nephrology, and the International Pediatric Transplant Association. The formal consensus reached is particularly significant in cases of weak or inconclusive evidence and where recommendations are based solely on expert opinion.
Activating ESR1 mutations are a major mechanism of resistance to aromatase inhibitors in hormone receptor-positive, HER2-negative metastatic breast cancer (mBC). International guidelines, including those from ASCO, NCCN, and ESMO, recommend liquid biopsy as the preferred approach for ESR1 mutation testing at progression on endocrine therapy, with digital PCR (dPCR) and next-generation sequencing (NGS) as the preferred analytical platforms. Although elacestrant was approved by the U.S. Food and Drug Administration together with Guardant360® Dx as its companion diagnostic, European regulatory frameworks allow the use of validated in-house assays for ESR1 testing, which are increasingly being implemented across clinical laboratories. To support the clinical implementation of ESR1 testing and improve analytical standardization in routine practice, we performed a European multicentre analytical verification study using dPCR- and NGS-based liquid biopsy workflows. Six referral institutions participated in this study. All laboratories verified dPCR workflows and four also verified NGS-based assays using standardized reference materials containing clinically relevant ESR1 mutations. Limit of detection (LoD) and limit of blank (LoB) were determined in each laboratory according to locally validated workflows following CLSI-based verification procedures. Analytical sensitivity and specificity were assessed across platforms, focusing on the two most frequently tested ESR1 hotspot mutations, p.Y537S and p.D538G. Total DNA input ranged from 10 to 30 ng per reaction for dPCR assays, while NGS input followed platform-specific requirements. LoD values ranged from 0.01% to 0.07% variant allele frequency (VAF) for dPCR assays and from 0.01% to 0.1% for NGS-based workflows, depending on platform characteristics and DNA input. Limit of blank values were low across laboratories, with minimal background signal detected in plasma samples from healthy donors. Comparable analytical performance was observed across different platforms when assays were performed under validated laboratory conditions. These results demonstrate that both dPCR and NGS-based liquid biopsy workflows can be successfully implemented for ESR1 mutation testing in routine clinical practice using locally validated assays. This multicentre verification study provides practical guidance on assay verification, DNA input requirements, and key analytical parameters required to ensure reliable ESR1 mutation detection across different European laboratories. Robust analytical verification of ESR1 testing may improve diagnostic reliability and support personalized treatment strategies for patients with hormone receptor-positive, HER2-negative metastatic breast cancer.
Interpersonal violence against children and adolescents constitutes a significant public health issue associated with substantial morbidity and long-term disability. This study utilizes Global Burden of Disease (GBD) 2023 estimates to quantify the burden of interpersonal violence injuries among the population <20 years of age across the 27 European Union countries (EU27). We analysed incidence and Years Lived with Disability (YLDs) for injury types and age groups (<5, 5-14, and 15-19 years). A 'Disability Drivers' analysis compared injury frequency against disability burden to identify priority areas. Long-term (1990-2023), mid-term (2010-2023), and short-term trends (2020-2023) were analysed to distinguish systemic risks from emerging threats. The analysis reveals geographical and temporal heterogeneity. In 2023, Hungary reported the highest incidence rate (1085.7 per 100 000; 95% UI: 917.6-1295.5), while Italy reported the lowest (131.9 per 100 000; 95% UI: 94.3-175.5). Despite low overall incidence, Italy exhibited short-term spikes (2020-2023) in severe trauma among children aged <5, with severe chest injuries rising by 79.1% (95% UI: 66.4%-92.3%). Long-term analysis identified systemic worsening in Eastern Europe, notably in Romania, where poisoning in children <5 years increased by 77.9% (95% UI: 55.5%-96.0%) since 1990. Violence-related injuries among children in the EU27 show a polarized pattern, with chronic burdens in Eastern Europe and emerging acute escalations in Southern Europe. Prevention strategies should consider both injury frequency and disability burden to effectively allocate resources.
Monoclonal antibodies (mAbs) have revolutionized therapeutic treatments by their ability to target specific antigens, leading to enhanced clinical outcomes over other drugs. They are one of the largest modalities within the growing biotherapeutics space and are indicated for a range of diseases. Though transformative, mAbs are still not readily accessible to many patients globally because of their high costs. An increasing number of mAbs are losing patent exclusivity, which has opened the door for the development of biosimilars that could drive down costs and ensure increased access to these life-saving drugs. Regulators approve biosimilars after conducting a rigorous evaluation similar to any other biologic medicine to ensure the safety, quality, and efficacy of these products. To establish biosimilarity, extensive comparative analytical and clinical studies of the biosimilar product with the approved reference product is a regulatory expectation. Growing acceptance from regulators to potentially waive clinical efficacy studies when robust evidence for similarity with reference product is established from analytical, functional, and pharmacokinetic/pharmacodynamic studies will have a major impact on reducing the time and cost of developing biosimilars. Comparative analytical assessment includes side-by-side analysis of the biosimilar with the reference product to demonstrate similarity regarding their physicochemical and functional characteristics. This is usually achieved by identifying product quality attributes (PQAs) that could impact clinical safety and efficacy and applying orthogonal analytical methods to characterize these attributes to identify any differences between the products. This review identifies the common PQAs studied for approved mAb biosimilars in the United States and the European Union through to the end of 2024. We have also compiled the data for the analytical methods used to characterize these attributes and identified a subset of methods universally used among biosimilar applicants. Finally, a brief overview of the risk-based analysis of attributes is summarized from the regulatory submissions.
National income level influences the prevalence and outcomes of cardiovascular disease (CVD), with lower-income countries contributing disproportionately to the global CVD burden. Chronic total occlusion (CTO) percutaneous coronary intervention (PCI) requires specialised equipment, increasing procedural costs. However, whether national income level contributes to disparities in managing patients with CTO remains unclear. To compare the clinical profiles, procedural settings and outcomes of patients undergoing CTO-PCI in middle-income countries (MICs) and high-income countries (HICs). This cross-sectional study included 15,329 patients who underwent CTO-PCI between 2021 and 2023. Data were obtained from the European Registry of Chronic Total Occlusions (ERCTO). Of the 24 enrolling countries, 7 were classified as MICs and 14 as HICs. Patients in HICs were older (67 ± 10 vs 61 ± 10 years; p < 0.001) and presented with greater CTO complexity (J-CTO score: 2.31 ± 1.25 vs 1.99 ± 1.17; p < 0.001). Conversely, patients in MICs were more likely to have diabetes (35% vs 29%; p < 0.001) and to be active smokers (59% vs 49%; p < 0.001). Patients in MICs had lower use of mechanical cardiac support (0.1% vs 0.8%; p < 0.001), advanced calcific plaque modification devices (1% vs 6.1%; p < 0.001), and intravascular ultrasound (14% vs 25%; p < 0.001). MICs achieved higher procedural success (89.5% vs 90.5%; p = 0.07) but higher mortality compared to HICs (0.6% vs 0.2%; p < 0.001). Among a selected population of patients undergoing CTO-PCI, notable clinical, anatomical, and procedural differences exist between MICs and HICs. These findings highlight the importance of tailoring public health strategies to optimise cardiovascular care across diverse economic settings.
Despite the demonstrated clinical benefits of poly(ADP-ribose) polymerase inhibitors (PARPis), up to 25% of newly diagnosed patients are nonadherent. To maximize clinical outcomes, there is a need to identify best practices used at centers of excellence that treat patients with advanced epithelial ovarian cancer (aEOC) with PARPis. A qualitative initiative was undertaken in which healthcare professionals (HCPs) from select centers of excellence in the European Union and North America were invited to complete an online survey, be interviewed, and participate in a virtual workshop. The 15-item survey asked questions about the factors comprising PARPi models of care at their center, the typical patient journey, and current treatment challenges. The interview and workshop were intended to gain additional insights and to further define the key components of care models, as well as factors contributing to long-term therapeutic success. Twelve centers of excellence, six in the European Union and six in North America, participated. Five factors were identified as contributing to PARPi models of care at the participating centers of excellence: (1) supportive infrastructure to optimize patient care, (2) best communication practices for HCPs, (3) HCP education and support to optimize patient care, (4) PARPi maintenance treatment initiation to support long-term adherence, and (5) PARPi maintenance treatment adherence and continuation. The creation of a compassionate, supportive healthcare environment is essential to maximizing the likelihood of patients with aEOC initiating, adhering to, and continuing with first-line maintenance treatment with a PARPi.
Patients with chronic thromboembolic pulmonary hypertension (CTEPH) were traditionally advised against exercise training, based on unsubstantiated concerns that exercise-induced increases in pulmonary blood flow might aggravate vascular remodeling and trigger right ventricular decompensation. This dogma has been overturned by robust clinical evidence demonstrating that supervised exercise and respiratory training are both safe and effective. Exercise interventions consistently improve functional capacity, pulmonary hemodynamics, and health-related quality of life. Reflecting this paradigm shift, the latest European Society of Cardiology/European Respiratory Society guidelines endorse structured rehabilitation as an integral adjunct to established pharmacologic and interventional therapies.
Chronic hepatitis delta (CHD) causes severe chronic viral hepatitis. This study examines the predictors and outcomes of CHD course in a large contemporary cohort. CHD patients with ≥3 years follow-up from the multicentre retrospective D-SOLVE and hepatitis D virus (HDV)-1000 database (6 European centres) were enrolled. Longitudinal changes in biochemical and laboratory markers were analysed. Time-to-event analysis was performed and predictors of liver-related events (LREs) were assessed with univariable and multivariable Cox regression analysis. Among a total of 1004 patients, 565 (56%) with ≥3 years follow-up were included. Patients had a mean (SD) age of 45 (12) years, with 55% men and 60% of European origin. At baseline, 77.8% were HDV RNA+, 39.8% had cirrhosis and 45% had previous interferon therapy. During a median (IQR) follow-up of 55 (46-62) months, 48 patients progressed to cirrhosis at 1, 3 and 5-year cumulative incidence of 1.8%, 5.6% and 13.6%, respectively. De-novo LREs occurred in 47 (9%) patients at 1, 3 and 5-year cumulative incidence of 0.8%, 2.4% and 10.8%, respectively. Cox regression analysis showed that anti-hepatitis C virus+ (adjusted hazard ratio (aHR)=1.72, 95% CI 1.22 to 5.88) and elevated gamma-glutamyl transferase (GGT) (aHR=2.77, 95% CI 1.22 to 6.27) at baseline were significantly associated with cirrhosis onset, while older age (aHR=1.03, 95% CI 1.00 to 1.07), elevated GGT (aHR=4.38, 95% CI 1.81 to 10.57), detectable HDV RNA (aHR=10.32, 95% CI 1.34 to 79.53) and cirrhosis diagnosis (aHR=2.23, 95% CI 1.03 to 4.84) correlated with LREs. The risk for LREs increased from HDV RNA ≥1000 IU/mL, while hepatitis B surface antigen (HBsAg) levels did not correlate with disease progression. In a large real-life cohort of CHD patients, older age, GGT elevation, cirrhosis and detectable HDV RNA were the main determinants of liver-related outcomes, with worse prognosis noted from HDV RNA ≥1000 IU/mL.
No study has systematically assessed the clinical appropriateness of tests in commercial direct-to-consumer (DTC) laboratory panels. We classified tests from major DTC platforms against screening guidelines and mapped the European regulatory landscape. Cross-sectional content analysis of 76 wellness panels (≥10 biomarkers) offered through the direct access testing (DAT) model from 12 platforms across seven countries (April 2026). Tests were standardized to Logical Observation Identifiers Names and Codes (LOINC) and classified into four tiers: beneficial (Tier 1), context-dependent (Tier 2), low-value waste (Tier 3), and cascade-driving harm (Tier 4 - false positives triggering biopsies, surgery, or imaging). Two blinded coders classified tests (Cohen's κ=0.71, linear weighted, below pre-specified κ≥0.80; 100 % agreement on Tier 4). Of 191 unique tests across 2,829 test-instances, 58.1 % (95 % confidence interval [CI] 51.0-64.9 %) were Tier 3 or 4. Nine tests (4.7 %), predominantly tumor markers, were Tier 4 cascade drivers. Tier 3 + 4 proportions varied across platforms (χ2=242.33, degrees of freedom [df]=11, p<0.001), from 2.8 % to 37.9 %. The largest panel generated 9.8 expected false positives per healthy consumer. The same multinational corporation operated under mandatory prescription in one EU country and unrestricted DTC access in another. Over half of tests in commercial DAT wellness panels lack screening evidence, and a subset - predominantly tumor markers - functions as documented cascade drivers in healthy individuals. The four-tier framework distinguishing waste from harm offers a tool for regulatory evaluation of DTC panel composition.
Biosimilars are a critical strategy for improving access to high-cost biologics and ensuring the sustainability of healthcare systems worldwide. Over the past decade, China has transformed from a nascent market into one of the world's most active regions for biosimilar development. This review evaluates this transformation with a focus on regulatory evolution, approval dynamics, and global integration. We trace the development of China's biosimilar regulatory framework from the foundational 2015 Technical Guidelines to the current system of 19 technical and product-specific guidelines, highlighting the maturation of a stepwise, science-driven comparability paradigm aligned with international regulatory standards. Drawing on a systematic analysis of 83 biosimilars approved between 2019 and 2025, we analyze trends across molecular classes, therapeutic areas, and regulatory review pathways, illustrating how regulatory expectations and sponsor development strategies have evolved through representative case examples. Notably, the 2025 annual reports from both the US Food and Drug Administration and European Medicines Agency emphasize the increasing number of biosimilar approvals, therefore, we place China's approval experience in brief comparative context. Finally, we discuss China's expanding biosimilar development pipeline in the context of the forthcoming global biologics patent cliff and ongoing international initiatives to streamline biosimilar development, highlighting China's increasing integration into the global biopharmaceutical landscape.
Dyeing wastewater is a significant source of industrial pollution, with emerging contaminants posing risks to aquatic ecosystems and human health, yet integrated assessments of multiple contaminant classes in dyeing wastewater at the enterprise scale remain scarce. This study investigated the occurrence, removal efficiency, and ecological risk of polyfluoroalkyl substances (PFAS), bisphenols (BPs), and phthalates (PAEs) in wastewater samplesfrom 18 dyeing enterprises in Guangdong Province, China. Detected concentrations ranged from 1.20-111 ng/L for PFAS, 10.5-1.98 ×103 ng/L for BPs, and 15-3.27 × 104 ng/L for PAEs, revealing significant inter-enterprise variability. Removal efficiencies varied substantially across enterprises, with some compounds exhibiting negative removal rates, indicating possible transformation, desorption, or process-induced release during treatment. Ecological risk assessment identified bisphenol A (BPA) and diethylhexyl phthalate (DEHP) as priority contaminants. Given the persistence and bioaccumulation potential of PFAS, additional risk assessment focused on fish collected near discharge points. While PFAS concentrations in some samples exceeded European Union regulatory thresholds, overall levels suggest limited short-term health risk, although potential long-term exposure remains a concern. Given its high concentration of dyeing enterprises and substantial wastewater discharge intensity, Guangdong represents a critical case for understanding dyeing wastewater impacts in China. The findings and solutions derived from this region are therefore not only locally relevant but also provide a valuable reference for dyeing industries across China.
Apical aneurysms in hypertrophic cardiomyopathy (HCM) have been linked to sudden cardiac death (SCD) and a nidus for thromboembolism. Uncertainty remains regarding the level of risk and significance of aneurysm size. The objective of the study was to determine the rate of SCD events and prevalence of apical thrombus or embolic events by size (maximum transverse dimension). Apical aneurysms were identified in 510 patients from 10 centers, followed a median of 4.1 years for SCD events (SCD, appropriate implantable cardioverter defibrillator therapy, and resuscitated SCD) or development of apical thrombus/thromboembolism. Relationship between size and SCD events was analyzed using multivariable Cox proportional hazard models. In 510 HCM patients: 19% had small aneurysms (<10 mm), 39% medium (10-19 mm), 39% large (20-39 mm), and 3% very large (≥40 mm). SCD event rate was 2.1%/year, with risk increasing with increasing aneurysm size: 0.2%/year in small, 2.3%/year in medium, 3.0%/year in large and 8.2%/year in very large (P < 0.001). On multivariable analysis, greater size was associated with SCD events, independent of other risk markers or European Society of Cardiology-SCD score. Either an embolic event (3.6% of patients) or apical thrombus (10% of patients) occurred in 13% of patients and was independently associated with greater aneurysm size, 3% in small to 25% in very large aneurysms (P < 0.001). In a large cohort of HCM patients with apical aneurysms, rates of SCD events were high, with continuous relationship between size and risk. Small aneurysms (<10 mm) were associated with low risk for SCD events (0.2%/year), whereas aneurysms ≥10 mm with high risk (>2%/year). Although embolic events were uncommon, increasing aneurysm size was associated with the prevalence of apical thrombi.
Aflatoxin B₁ (AFB₁), a potent natural carcinogen, poses a severe and widespread threat to global food safety and public health. To address this challenge, the rational design of robust artificial catalysts for efficient AFB₁ degradation represents a promising strategy. Inspired by the multicopper active center of natural laccase, we herein fabricated high-performance metalloenzyme mimics via a biomimetic interfacial co-assembly strategy for efficient AFB1 degradation. De novo designed peptides, incorporating histidine and cysteine as cooperative metal-binding motifs within a self-assembling LK peptide framework, underwent coordinative co-assembly with Cu²⁺ ions. Driven by synergistic metal-ligand interactions-primarily the imidazole groups of histidine and thiol groups of cysteine-the assembly process enabled the formation of well-defined, copper-enriched catalytic interfaces that accurately recapitulated the geometric architecture and electronic structure of laccase's active center, yielding peptide-copper colloidal nanoassemblies with remarkable laccase-mimicking activity. In comparison with natural laccase, the optimized metalloenzyme mimic displayed superior catalytic efficiency, as well as enhanced pH tolerance and thermal stability, enabling complete degradation of AFB₁ within 90 min under optimal conditions. The transformation products of AFB₁ showed markedly reduced cytotoxicity relative to parent mycotoxin. Importantly, the metalloenzyme mimic exhibited excellent practical performance, efficiently degrading AFB₁ in contaminated grain and nut samples and reducing residual concentrations to meet the strict safety limits set by the European Union. This work not only provides a potent biocatalyst for mycotoxin remediation but also elucidates a fundamental co-assembly pathway for engineering functional colloidal materials with tailored catalytic interfaces, offering broad implications for designing bio-inspired solutions in environmental and food chemistry.
The recommendations of the European association of urology (EAU) suggests treating the bladder phenotype with Hunner's lesion (HL) associated with bladder pain syndrome (BPS) by transurethral resection (TUR) or coagulation of the lesions. We present the results of this approach in our practice. Retrospective monocentric study including consecutive patients presenting BPS with HL assessed during cystoscopy between 1998 and 2026. Patients were divided in two groups according to treatment strategy: group 1 with medical management (association of Cimetidine or bladder instillations of RIMSO or Pentosan polysulfate de sodium (CRP)) and group 2 with surgical management (immediate TUR, repeated if pain and HL recurrence). The primary objective was to compare success of each management strategy, defined by complete resolution of pain. Secondary objectives were to describe efficacy on pollakiuria symptoms and morbidity of surgical management. Thirty-two patients were included (group 1 n=9, group 2 n=23). Success of treatment was achieved in 11.1% (1/9) cases in group 1 and in 78,2% (18/23) cases in group 2 (p=0.001). In group 1, the only pain resolution was observed after RIMSO bladder instillation. In group 2, 61,1% (11/18) experienced a pain recurrence after being cured with a median delay of 13 [6-30.25] months. 12 patients required a 2nd TUR. Resolution of pollakiuria occurred in 0% in group 1 and 34,8% (8/23) in group 2 (p=0.07). Three patients required reintervention after TUR, 2 for bladder perforation (1 open and 1 laparoscopic bladder repair), 1 for gross haematuria requiring coagulation and 12.5% (4/32) patients ultimately underwent cystectomy. in case of BPS with a bladder phenotype and one or more Hunner's lesions, treatment by transurethral resection of the inflammatory lesion is more effective for pain and, to a lesser extent, for pollakiuria than our usual medical treatment (CRP) but does not prevent recurrence after varying periods of time.
Paediatric regional anaesthesia (RA) is a safe and effective modality for peri-operative pain management, associated with improved outcomes and reduced opioid use. However, utilisation remains variable, and defining appropriate benchmarks is challenging. We conducted a 28-day retrospective audit of RA practice in a tertiary paediatric centre. All anaesthesiologist-performed regional blocks were recorded. Surgical cases not typically amenable to RA were excluded. The primary outcome was the proportion of patients receiving RA, with secondary analysis excluding unsuitable procedures. A total of 491 patients underwent surgery, of whom 94 (19.1%) received RA, increasing to 20.8% following case exclusion. A total of 117 blocks were performed, comprising 86 peripheral (73.5%) and 31 central (26.5%) blocks. Peripheral techniques included 42 lower limb (35.9%), 30 truncal/craniofacial (25.6%), and 14 upper limb (12.0%) blocks. Central blocks included 15 caudal (12.8%), 10 epidural (8.5%), and 6 paravertebral (5.2%) blocks. RA utilisation in our institution is consistent with European data. These findings establish a local benchmark and support ongoing audit and quality improvement in paediatric anaesthesia practice.
Cutaneous melanoma poses a growing global health concern, with solar ultraviolet radiation (UVR) as its main risk factor. Outdoor workers may be at increased risk due to prolonged occupational solar UVR exposure, but evidence remains limited. To examine the risk of melanoma associated with occupational solar UVR exposure in a nationwide cohort of Danish workers. Using Danish national registers, we established a cohort of all individuals employed between 1977 and 2015 and linked occupational histories to first-time melanoma diagnoses in the Danish Cancer Registry. Cumulative occupational solar UVR exposure was estimated by matching occupational histories to a European job exposure matrix and expressed as cumulative standard erythema dose (SED)-years. Incidence rate ratios (IRRs) for cutaneous melanoma were calculated using discrete-time hazard models, and exposure-response relations were further examined with restricted cubic splines. We adjusted for age, sex, calendar year, smoking, dermatological or immunological disease, organ transplantation, parental history of melanoma and medications. Among 2.9 million workers followed for a median of 19 years, 11,344 workers developed cutaneous melanoma. The median cumulative occupational solar UVR exposure was 5.99 SED-years. Melanoma incidence increased with increasing cumulative exposure, reaching a peak IRR of 1.59 (1.43-1.76) at 14.80 SED-years in the spline analysis, and with an adjusted IRR of 1.57 (95% CI: 1.43-1.71) for workers in the highest vs. the lowest exposure quartile. Occupational solar UVR exposure was associated with an exposure-response relation increase in melanoma risk. These findings highlight the urgent need for workplace sun-protection policies.
The purpose of this study is to compare the answers of the 12 most frequently asked questions regarding breast augmentation surgery on both Google Gemini and ChatGPT-4.5. Our research highlights the growing importance and differential performance of artificial intelligence models in informing patients before surgery. The 12 most asked questions about breast augmentation, based on user engagement metrics, were obtained from the Realself website. These twelve questions were investigated on both Google Gemini and ChatGPT-4.5. Information received from both platforms was analyzed and evaluated by ten plastic surgeons with European Board of Plastic Reconstructive and Aesthetic Surgery (EBOPRAS) certification. The surgeons, who reached a consensus on the application of the Global Quality Score (GQS) scale prior to evaluation, were blinded to the source of the answers. The GQS scale was used for the evaluation. The average results obtained were compared with each other. While the average of Google Gemini responses was calculated at 2.842, the average of ChatGPT-4.5 responses was calculated at 3.867. For this calculation, the Wilcoxon signed-rank test was used. It was found that the ChatGPT-4.5 responses were statistically superior to Google Gemini according to the Global Quality Score (GQS) (p = 0.003). While there is emerging research on AI in plastic surgery, studies specifically comparing ChatGPT and Gemini for breast augmentation patient education using a blinded evaluation by board-certified surgeons remain limited. We suggest that AI-powered chatbots offer significant advantages for patient education but should be used cautiously. While ethical concerns persist, this study underscores the practicality of ChatGPT in informing patients about plastic surgery procedures, emphasizing the need for careful usage and collaboration to optimize benefits while minimizing risks. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
Parental distress impacts children's emotional adjustment, highlighting the need to identify protective factors. Promising candidates include positive control (i.e., autonomy support, indexed by parental encouragement, praise, and open-ended questions) and representational mind-mindedness (the propensity for parents to view children as independent agents). To counterbalance the focus on European and North American samples, we included 849 parent-child dyads from England, Hong Kong and Mainland China (Mchild age = 5.17 years, SD = 0.51). Parents rated their own distress and child internalizing problems; their interactions with their children were assessed for positive control, and their speech samples were coded for representational mind-mindedness. In a single-paper meta-analysis, parental distress was associated with elevated child internalizing problems and low positive control consistently across sites, but only associated with low mind-mindedness in England. Within-site analyses showed that intergenerational associations in distress-internalizing problems were attenuated by positive control in Mainland China and by mind-mindedness in England; multi-group modeling demonstrated that this latter effect was site-specific. These findings highlight the importance of widening the cultural scope of this research field.
Coccidiosis remains a major constraint in poultry production; therefore, this study evaluated the anticoccidial efficacy of a phytogenic blend of cinnamon bark and Rumex nervosus leaf in Eimeria tenella-challenged broilers. Birds were assigned to six treatments: low (PL-C), medium (PM-C), and high (PHC) phytogenic, a standard anticoccidial (STD-C), an infected untreated control (IUC), and an unchallenged untreated control (UUC). All groups except UUC were orally challenged on day 15 with 2 × 104 sporulated Eimeria tenella oocysts per bird, and performance and anticoccidial responses were evaluated during 7 days post-inoculation (DPI). The phytogenic blend was selected for the complementary biological activities of cinnamon and Rumex nervosus and was characterized by abundant phenolic compounds, particularly gallic acid and cinnamaldehyde derivatives, associated with antiparasitic, antioxidant, antimicrobial, and gut-protective effects. Infection markedly impaired growth performance, feed efficiency, performance index, and European production efficiency factor in the IUC group. Dietary phytogenic supplementation alleviated these adverse effects (P < 0.05) by reducing oocyst output (24.2-31.0%), increasing oocyst inhibition rates (69.0-75.8%), and lowering lesion severity and bloody diarrhea scores compared with IUC. Among phytogenic treatments, PHC exhibited the strongest anticoccidial activity, with the lowest oocyst counts and improved cecal morphometric recovery, particularly reduced cecal wall thickness, whereas PL-C showed the greatest improvement in body weight gain and production performance among phytogenic groups. Anticoccidial index values indicated marked anticoccidial activity for phytogenic treatments (162.3-167.8) and excellent activity for STD-C (187.5), compared with inactive status in IUC (83.6). Phytogenic supplementation also improved cecal integrity through increased villus height, reduced crypt depth, and enhanced villus height-to-crypt depth ratio, indicating improved absorptive capacity and mucosal recovery. Overall, the cinnamon- Rumex nervosus blend effectively mitigated Eimeria tenella-induced damage and demonstrated strong potential as a natural alternative to conventional anticoccidials, although its efficacy remained slightly lower than the standard drug treatment.
There is conflicting evidence regarding the merits of patellar resurfacing during total knee replacement (TKR), as previous randomised controlled trials (RCTs) have been under-powered and with follow-up of ten years or less. A pragmatic, multicentre, open-label RCT was initiated in 1999 in the UK. Within a partial-factorial design, participants were randomly allocated to receive or not receive patellar resurfacing during primary TKR and were followed up for 20 years. Adult (aged ≥18 years) patients due to have a primary TKR under the care of a collaborating surgeon were eligible. Participants were allocated (1:1) using an automated telephone service stratified by surgeon, with minimisation according to the patients' age (<60 years, 60-79 years, ≥80 years), sex, and location of d isease. The primary outcome measure was the Oxford Knee Score (OKS), analysed using repeated measures mixed-effects linear regression analysis with marginal differences reported. Secondary measures included the 12-Item Short Form Health Survey (SF-12), the European Quality of Life 5-Dimensions 3-Levels (EQ-5D-3L), costs, cost-effectiveness, and subsequent knee surgery. This trial is registered with ISRCTN Registry, ISRCTN45837371. Between April 8, 1999, and Jan 13, 2003, 1715 participants (955 female and 760 male; mean age 70 years [SD 8], mean BMI 29·7 kg/m2) were randomly assigned: 861 to patellar resurfacing and 854 to no resurfacing. At the 20-year follow-up, 132 participants in the patellar resurfacing group and 110 participants in the non-resurfacing group provided outcome data, although marginal differences included earlier data for participants who died or had missing 20-year data. The marginal difference in OKS over the whole 20-year follow-up was 0·76 (95% CI -0·08 to 1·59; p=0·076) in favour of patellar resurfacing. During the 20-year follow-up period, although not significant, differences in OKS, SF-12, and EQ-5D-3L, readmissions, minor or intermediate operations, patella-related operations, major operations, and complications all favoured patellar resurfacing. At 20 years, the resurfaced group accrued significantly more quality-adjusted life-years (QALYs) than the non-resurfaced group (7·295 vs 6·884; difference 0·380, 95% CI 0·061 to 0·700; p=0·020). However, QALY differences were smaller in a sensitivity analysis assuming no difference in mortality (7·209 vs 6·964; difference 0·183, 95% CI -0·034 to 0·400; p=0·10). The cost of readmissions was non-significantly lower in the resurfaced group and offset the higher cost of primary TKR; therefore, overall 20-year health-care costs per participant were similar (£10 825 vs £10 889; difference -£6, 95% CI -£721 to £708; p=0·99). There was no significant difference in primary outcome (OKS) or other clinical endpoints. However, as clinical differences tend to support patellar resurfacing, the resurfacing group had significantly higher QALYs. There was no difference in costs over the 20-year period, and patellar resurfacing had a 99% probability of being cost-effective at any threshold above £10 000 per QALY gained. The evidence is therefore weighted towards resurfacing being the approach of first choice. UK National Institute for Health and Care Research Health Technology Assessment Programme.