Search Results (3,193)

Background and Objectives: The treatment of duodenal injuries remains one of the most challenging issues in clinical surgery due to their high morbidity and mortality rates. The primary objective of this study was to evaluate the histopathology and other diagnostic outcomes of wound repair following surgical reconstruction of large experimental duodenal defects using synthetic (ePTFE, expanded polytetrafluoroethylene) or organic (JSP, jejunal serosal patch) materials. Materials and Methods: A total of 20 European rabbits were randomly divided into two equal groups (n = 10 each). A grade III defect covering over 50% of the duodenum’s circumference was created in the second part of the duodenum of the rabbits. The anesthesia, duodenal injury, postoperative care, and animal sacrifice protocols were identical for all experimental rabbits. The effectiveness of JSP and ePTFE patch repair techniques was investigated based on clinical, macroscopic, and microscopic assessments at two and four weeks postoperatively. Results: Survival rates were comparable between groups (p > 0.05). Remarkable mucosal regeneration was evident in all experimental animals by two weeks, showing complete coverage of the jejunal serosal and ePTFE patches by re-epithelialized mucosa with functional villus formation. While partial development of the underlying muscular and serosal layers was observed in both groups at four weeks, the JSP group achieved a significantly higher median histological score (19 vs. 14; p = 0.003). Conversely, the ePTFE group exhibited a major safety concern: a highly significant increase (p ≤ 0.001) in Grade 4 dense, inseparable adhesions throughout the abdominal cavity, which were entirely absent in the JSP group. Conclusions: Both JSP and ePTFE are viable for duodenal reconstruction, but the autologous JSP is superior in tissue healing and safety. Severe adhesions associated with ePTFE constitute a significant clinical concern, limiting its use to a second-line alternative. Consequently, JSP is the preferred option, while ePTFE requires further long-term safety validation. Full article

Background/Objectives: Endoscopic submucosal dissection (ESD) is a state-of-the-art en bloc resection for early gastro-intestinal cancers and precursors developed and validated in Japan. Western expertise with this complex technique remains limited. Tutored training might be optimal for patients and ESD learning. We established ESD tutoring courses led by experienced Japanese experts to provide (i) optimal long-term curative outcomes and low complication rates for patients and (ii) hands-on training on difficult lesions for European endoscopists under direct expert supervision. Methods: Prospective data from 2011 to 2015 (follow-up to 12/2024) were analyzed. A total of 118 neoplasms (50% HGIEN and cancer) in 101 patients (median age 68 [37–91] years; 38% with significant comorbidities) were treated with expert or tutored ESD. Japanese experts performed 28 ESDs, while 22 trained beginners conducted 90 supervised procedures on difficult lesions during 5 live and 20 tutoring events (1–4 days each). Results: Analysis of the complete data showed curative and en bloc resection rates of 88% and 95%, respectively, with no recurrence after R0 resections during a median follow-up of 9.8 [1.5–14.9] years. Long-term survival remained recurrence-free after endoscopic resection of 3 recurrent adenomas (at R1/Rx) and curative surgery/2nd ESD for 5 non-curative ESDs. Adverse events occurred in 9.3% without emergency surgery or 30-day mortality. Comparing expert-only vs. tutored ESD procedures, beginners correctly applied curative ESD indications in 94% of 118 neoplasms. Experts resected larger lesions (22 cm²) at a rate of 9.3 cm²/h in 121 min. Tutored beginners achieved a 75% [25–100] self-completion rate on 33% smaller lesions in 112 min. Conclusions: ESD tutoring courses led by Japanese experts ensure excellent patient outcomes and standardized procedural training. This model may foster professional ESD performance across European referral centers. Full article

This paper introduces a novel extension of the classical Lindley distribution, termed the X-Lindley model, obtained by a specific mixture of exponential and Lindley distributions, thereby substantially enriching the distributional flexibility. To enhance its inferential scope, a comprehensive reliability analysis is developed under a generalized progressive hybrid censoring scheme, which unifies and extends several traditional censoring mechanisms and allows practitioners to accommodate stringent experimental and cost constraints commonly encountered in reliability and life-testing studies. Within this unified censoring framework, likelihood-based estimation procedures for the model parameters and key reliability characteristics are derived. Fisher information is obtained, enabling the establishment of asymptotic properties of the frequentist estimators, including consistency and normality. A Bayesian inferential paradigm using Markov chain Monte Carlo techniques is proposed by assigning a conjugate gamma prior to the model parameter under the squared error loss, yielding point estimates, highest posterior density credible intervals, and posterior reliability summaries with enhanced interpretability. Extensive Monte Carlo simulations, conducted under a broad range of censoring configurations and assessed using four precision-based performance criteria, demonstrate the stability and efficiency of the proposed estimators. The results reveal low bias, reduced mean squared error, and shorter interval lengths for the XLindley parameter estimates, while maintaining accurate coverage probabilities. The practical relevance of the proposed methodology is further illustrated through two real-life data applications from engineering and physical sciences, where the XLindley model provides a markedly improved fit and more realistic reliability assessment. By integrating an innovative lifetime model with a highly flexible censoring strategy and a dual frequentist–Bayesian inferential framework, this study offers a substantive contribution to modern survival theory. Full article

Background: Direct selective laser trabeculoplasty (DSLT) is a novel option for intraocular pressure (IOP) control in patients with glaucoma or ocular hypertension. The automated and touchless translimbal delivery of laser energy to 360 degrees of the trabecular meshwork (TM) improves aqueous outflow and lowers IOP. DSLT is faster, simpler, and less invasive than routinely performed SLT. Few studies have compared the two techniques. Objective: To retrospectively compare the safety and efficacy of DSLT and SLT over a 1-year follow-up period. Methods: In total, 16 eyes that underwent DSLT and 16 eyes that underwent SLT were included. The primary outcome measures were mean absolute and percent IOP reduction, number of medications, and BCVA at 1, 3, 6, and 12 months. Survival analysis on 1-year data was performed based on the presence of one or more of the following failure criteria: (1) IOP > 21 mmHg or less than 20% reduction in IOP from baseline at two consecutive visits; (2) increase in the number of IOP-lowering drops from baseline at two consecutive visits; (3) further procedures. Results: The survival rates in the DSLT vs. SLT group were 81% vs. 78%, 44% vs. 62%, and 37% vs. 43% at 3, 6, and 12 months, respectively. No statistically significant differences were reported. DSLT does not seem inferior to conventional SLT in terms of safety and efficacy in reducing IOP. Conclusions: The advantages of an automated, rapid, contactless technique may enlarge the cohort of patients eligible for a drop-free first-line IOP control procedure. Full article

Background: Pancreatic cancer (PC) has a very poor 5-year survival and prognosis. Even when CT or MRI shows no metastasis, staging laparoscopy(SL) still detects tiny peritoneal deposits in 20–30% of patients, making them ineligible for surgery. SL is invasive, requiring general anesthesia and substantial resources. Endoscopic ultrasound (EUS) allows the observation of the bile ducts, pancreas, and abdominal cavity, and EUS-guided fine-needle aspiration (EUS-FNA) is essential for pathological diagnosis. Reports on using EUS to perform peritoneal lavage cytology are currently not available. We hypothesized that combining EUS-FNA with peritoneal lavage (EUS-lavage technique; EUS-LT) could enhance staging accuracy and avoid unnecessary surgical procedures. Methods: Ten ex vivo porcine models underwent EUS-LT. Using a 19G FNA needle, 800 mL saline was instilled into the intraperitoneal cavity and then recovered. Two refinements were introduced sequentially: an ENBD catheter with additional side holes and, subsequently, a side-hole introducer (EndoSheather) that eliminated balloon dilation. The primary endpoint was procedural success. Secondary endpoints included safety, complications, recovered volume, duration of endoscopic procedure, and time required to instill 800 mL. Nonparametric tests compared outcomes across iterations. Results: Ten-model porcine ex vivo model series were included, and all procedures were successful. No device malfunctions or unanticipated technical failures; one minor mucosal injury during saline injection resolved after re-puncture. The average procedure time was 31.1 min. Stepwise refinements shortened procedure and infusion times and increased recovered volume. Recovered volume approached the instilled amount in later cases, indicating efficient performance. Conclusions: In this ten-model ex vivo series, EUS-LT demonstrated technical feasibility and short-term safety. Full article

The structural application of Fiber-Reinforced Polymers (FRP) is significantly hindered by their inherent thermal sensitivity. This paper presents a comprehensive review of the fire performance of FRP materials and FRP-concrete systems, spanning from material-scale degradation to structural-scale response. Distinct from previous studies, this review explicitly distinguishes between the fire behavior of internally reinforced FRP-reinforced concrete members and externally applied systems, including Externally Bonded Reinforcement (EBR) and Near-Surface Mounted (NSM) techniques. The thermal and mechanical degradation mechanisms of FRP constituents—specifically reinforcing fibers and polymer matrices—are first analyzed, with a focused discussion on the critical role of the glass transition temperature T_g. A detailed comparative analysis of the pros and cons of organic (epoxy-based) and inorganic (cementitious) binders is provided, elaborating on their respective bonding mechanisms and thermal stability under fire conditions. Furthermore, the effectiveness of various fire-protection strategies, such as external insulation systems, is evaluated. Synthesis of existing research indicates that while insulation thickness remains the dominant factor governing the fire survival time of EBR/NSM systems, the irreversible thermal degradation of polymer matrices poses a primary challenge for the post-fire recovery of FRP-reinforced structures. This review identifies critical research gaps and provides practical insights for the fire-safe design of FRP-concrete composite structures. Full article

Invasive Candida infections in the neonatal intensive care unit (NICU) are associated with significant morbidity and mortality, particularly among extremely preterm neonates. Early treatment with antifungals is critical to improve survival rates and avoid long-term adverse outcomes. Prevention with antifungal prophylaxis in high-risk neonates has been shown to reduce the prevalence of invasive Candida infections effectively. However, the irrational and/or inappropriate use of antifungals has been documented. This narrative review aims to provide an overview of the rationales for the inappropriate use of antifungals in the NICU, the consequences that ensue, and the promising strategy of antifungal stewardship programs to optimize antifungal use. The nonspecific clinical presentation of systemic Candida infections and the lack of rapid, accurate diagnostic techniques for Candida identification and specification in most settings lead to a high rate of empirical treatment in neonates without a proven infection. Moreover, evidence on the optimal dosing of antifungal agents and the treatment duration in the neonatal population is lacking, which may result in excessive or subtherapeutic drug exposure. Antifungal misuse is associated with microbiological consequences, including the emergence of antifungal-resistant Candida strains, and clinical consequences, such as drug toxicities and alterations in the intestinal mycobiome. It is therefore imperative to optimize antifungal use in the NICU. The implementation of antifungal stewardship programs, which, through a multidisciplinary approach, aim to improve diagnosis and guide clinicians on antifungal selection, dosing, and duration for both prevention and treatment according to the local epidemiology, represents a promising strategy for antifungal optimization in the NICU. Full article

Small pelagic fish, including sardines, are essential to global fisheries and aquaculture feed production. However, these species are increasingly exposed to intense exploitation. In Chile, the common sardine (Strangomera bentincki), endemic to the Humboldt Current System, supports major industrial and artisanal fisheries. Landings are expected to reach 300,000 tons by 2025, mostly for fishmeal production. As a keystone species, S. bentincki is highly sensitive to environmental variability during early development, which can reduce recruitment and threaten long-term population sustainability. This interdisciplinary approach integrates ecological and biotechnological perspectives to assess the feasibility of controlled juvenile sardine production in land-based Ecological Aquaculture (EA) systems, including Recirculating Aquaculture Systems (RAS) and Integrated Multi-Trophic Aquaculture (IMTA), which are designed to reduce environmental impacts. These systems enable precise control of temperature, feeding regimes, and water quality, facilitating investigations into larval and juvenile survival, growth performance, and physiological responses under variable thermal and nutritional conditions. Emphasis is placed on fatty acid metabolism during ontogeny, particularly docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), which are essential for somatic growth, reproductive development, and thermal tolerance. Developing standardized protocols for juvenile S. bentincki culture addresses key gaps in husbandry and physiology (temperature threshold, nutrient density, larval growth rate, etc.) while introducing a novel ecological–aquaculture integration framework. This approach links early-life ecology with applied rearing techniques to support stock enhancement, strengthen artisanal fisheries, and promote sustainable aquaculture diversification under increasing environmental variability. Full article

Background/Objectives: Endoscopic biliary stenting is the standard palliative intervention for malignant biliary obstruction, aimed at restoring ductal patency. Radiofrequency ablation (RFA) has been introduced as an adjunct technique to improve stent durability and patient outcomes. However, the literature remains inconclusive regarding which patients are most likely to benefit from the combination of RFA and stenting. Methods: We retrospectively described clinical outcomes of 24 patients undergoing endobiliary RFA combined with biliary stenting for malignant biliary obstruction. Post-procedural and 6-month outcomes were assessed using technical success and changes in serum bilirubin; procedure-related adverse events were extracted from available medical records. Results: Nineteen females and five males were included in the study. The most prevalent diagnoses were metastatic adenocarcinoma (n = 8) and cholangiocarcinoma (n = 6). 25% of patients did not complete the 6-month follow-up due to malignancy progression. 16 out of 18 maintained the patency of biliary stents. Repeat endoscopic intervention for suspected stent dysfunction was documented in one patient. When analyzed in an intention-to-treat manner (counting deaths before 6 months as failures), the corresponding 6-month patency/clinical success rate was 16/24 (66.7%). Conclusions: In this retrospective single-center experience, RFA combined with biliary stenting was feasible and was associated with maintained biliary drainage in a majority of patients who survived to the 6-month assessment. Full article

Organoids are three-dimensional multicellular structures that mimic key aspects of native tissues consisting ideal tools to study organ development and pathophysiology when incorporated in customized bioscaffolds. In vivo, the extracellular matrix (ECM) maintains tissue integrity and regulates cell adhesion, migration, differentiation, and survival through biochemical and mechanical signals. Tissue-derived decellularized extracellular matrix (dECM) can preserve organ-specific biochemical signals and cell-adhesive motifs, creating a bioactive environment that supports physiologically relevant organoid growth. 3D bioprinting technology marks a transformative phase in organoid research by enhancing the structural and functional complexity of organoid models and expanding their application in pharmacology and regenerative medicine. These systems enhance tissue modeling and drug testing while adhering to the principles of animal replacement, reduction, and refining (3Rs) in research. Remaining challenges include donor variability, limited mechanical stability, and the lack of standardized decellularization protocols that can be addressed by adopting quality and safety metrics. The combination of dECM-based biomaterials and 3D bioprinting holds great potential for the development of human-relevant, customizable, and ethically sound in vitro models for regenerative medicine and personalized therapies. In this review, we discuss the latest (2021–2025) developments in applying extracellular matrix bioprinting techniques to organoid technology, presenting examples for the most commonly referenced organoid types. Full article

Introduction: While extensive research has been conducted on specific factors affecting transplant outcomes in simultaneous pancreas-kidney recipients, less is known about outcomes following single pancreas transplantation (PTx). This study focuses on identifying factors related to early graft loss after PTx. Patients and Methods: A retrospective analysis was performed on a Eurotransplant (ET) registry database encompassing all consecutive solitary pancreas transplantations from 2000 to 2018. To address any missing values, multiple imputation techniques were employed. Uni and multivariable statistical analyses were performed. Results: The primary causes of early graft loss (<90 days) were thrombosis, bleeding, rejection, and infection. Using multivariable analysis, donor male gender (Hazard Ratio (HR) 0.62) was significantly associated with early graft survival. Of all recipient variables, recipient age (HR 0.96) and recipient cardiovascular history (HR 2.10) were associated with graft loss. A subgroup analysis PTx of female donors into female recipients showed an increased risk for early graft loss compared to male-to-male transplants (HR 2.14). The graft survival rates were 62.9% and 79.0%, respectively (p = 0.017). Discussion: This Eurotransplant registry analysis identifies various donor- and recipient-related risk factors after PTx, partly mirroring the SPK population but also identifying new factors. These findings identify PTx patients as a separate entity in pancreas transplantation and emphasize the need for tailor-made matching of donors and recipients. Full article

Lung cancer ranks among the world’s most prevalent and deadly diseases. Early detection is crucial for improving patient survival rates. Computed tomography (CT) is a common method for lung cancer screening and diagnosis. With the advancement of computer-aided diagnosis (CAD) systems, deep learning (DL) technologies have been extensively explored to aid in interpreting CT images for lung cancer identification. Therefore, this review aims to comprehensively examine DL techniques developed for lung cancer screening and diagnosis. It explores various datasets that play a crucial role in lung cancer CT image segmentation and classification tasks, analyzing their differences in aspects such as scale. Next, various evaluation metrics for measuring model performance are discussed. The segmentation section details convolutional neural network-based (CNN-based) segmentation methods, segmentation approaches using U-shaped network (U-Net) architectures, and the application and improvements of Transformer models in this domain. The classification section covers CNN-based classification methods, classification methods incorporating attention mechanisms, Transformer-based classification methods, and ensemble learning approaches. Finally, the paper summarizes the development of segmentation and classification techniques for lung cancer CT images, identifies current challenges, and outlines future research directions in areas such as dataset annotation, multimodal dataset construction, multi-model fusion, and model interpretability. Full article

Background: Minimally invasive pancreatoduodenectomy (MIPD) has evolved from an experimental technique to a feasible surgical option for pancreatic cancer in selected settings. However, its oncologic adequacy, safety, and generalizability remain debated, particularly given the biological aggressiveness of pancreatic ductal adenocarcinoma (PDAC) and the technical complexity of the procedure. Methods: This narrative review critically summarizes contemporary evidence regarding MIPD for pancreatic cancer, with particular attention to randomized controlled trials (RCTs), meta-analyses, and large observational studies. We distinguish findings derived from mixed periampullary tumor cohorts from those specific to PDAC and evaluate methodological limitations, learning-curve effects, and sources of heterogeneity across studies. Results: Recent RCTs and meta-analyses demonstrate that, when performed by experienced surgeons in high-volume centers, MIPD achieves perioperative outcomes comparable to open pancreatoduodenectomy, with advantages including reduced blood loss, shorter hospital stay, and faster functional recovery. Importantly, oncologic parameters such as R0 resection rates and lymph node yield appear equivalent between approaches, although robust long-term survival data from PDAC-specific RCTs remain lacking. Emerging evidence supports the feasibility of MIPD in complex clinical scenarios, including after neoadjuvant therapy, in frail or elderly patients, and in selected cases requiring vascular resection. Nonetheless, outcomes are strongly influenced by surgeon experience, institutional volume, and patient selection. Cost-effectiveness analyses and data from lower-volume centers remain limited. Conclusions: Current evidence supports MIPD as a viable alternative to open surgery for pancreatic cancer in carefully selected patients treated at specialized centers. However, claims of oncologic superiority are premature. Future research should focus on PDAC-specific randomized trials, standardized quality metrics, and strategies to mitigate learning-curve and resource-related barriers to broader implementation. Full article

Introduction: Radiotracer-based nuclear imaging, including positron emission tomography (PET) and single-photon emission computed tomography (SPECT), can complement conventional cross-sectional imaging in renal cell carcinoma (RCC) by providing biological characterisation of tumour metabolism, angiogenesis, hypoxia, and the tumour microenvironment. While computed tomography (CT) and magnetic resonance imaging (MRI) remain the diagnostic standard, accumulating evidence suggests that selected nuclear imaging techniques may offer incremental value in specific clinical scenarios. Methods: A narrative literature review was performed using PubMed, Embase, and Web of Science to identify preclinical, retrospective, and prospective studies evaluating PET and SPECT radiotracers in localised and metastatic RCC. Priority was given to meta-analyses, multicentre prospective trials, and studies with histopathological correlation. Results: [¹⁸F]fluorodeoxyglucose (FDG) PET/CT demonstrates limited sensitivity for primary renal tumours (pooled sensitivity of approximately 60%) but performs substantially better in metastatic and recurrent disease (pooled sensitivity and specificity of approximately 85–90%), where uptake correlates with tumour grade, progression-free survival, and overall survival. [^99mTc]sestamibi SPECT/CT differentiates oncocytoma and hybrid oncocytic/chromophobe tumours from malignant RCC with pooled sensitivity and specificity of around 85–90%, supporting its role in evaluating indeterminate renal masses rather than staging. Prostate-specific membrane antigen (PSMA) PET/CT shows high detection rates in clear-cell RCC, particularly in metastatic disease, with reported sensitivities of approximately 85–90% and management changes in up to 40–50% of selected cohorts. Carbonic anhydrase IX (CAIX)-targeted PET/CT enables the biologically specific visualisation of clear-cell RCC, achieving sensitivities and specificities in the range of 85–90% in prospective phase II and III trials for primary tumour characterisation. Fibroblast activation protein inhibitor (FAPI) PET/CT demonstrates high tumour-to-background uptake in early RCC studies, but evidence remains preliminary, with small cohorts and recognised non-specific uptake in benign inflammatory and fibrotic conditions. Conclusions: Radiotracer-based nuclear imaging provides complementary, biology-driven insights in RCC that extend beyond anatomical assessment. While most modalities remain adjunctive or investigational and are not recommended for routine use, selective application in carefully chosen clinical scenarios may enhance tumour characterisation, prognostication, and personalised treatment planning. Full article

Background/Objectives: In type 2 diabetes (T2DM), dysregulated glucose and lipid metabolism impair cellular energy sensing and inhibit autophagy, leading to the accumulation of dysfunctional cellular components, increased inflammation and oxidative stress, and activation of the intrinsic apoptotic pathway. Prepared Rehmannia glutinosa is an anti-diabetic traditional Chinese medicine whose active monomers, including 5-Hydroxymethylfurfural (5-HMF) and isoverbascoside, exhibit potential antioxidant and anti-apoptotic effects. However, their role in β-cell protection remains unexplored. This study aims to investigate the protective mechanisms of 5-HMF and isoverbascoside against H₂O₂-induced oxidative damage in pancreatic β-cells. Methods: INS-1 and MIN6 β-cells were treated with 5-HMF and isoverbascoside (20 μM, 40μM) for 24 h under H₂O₂-induced oxidative stress. Multiple techniques were employed, including transcriptomics, proteomics, machine learning, Western blot analysis, and molecular docking. Flow cytometry and Hoechst 33342 staining were used to assess apoptosis, while autophagy was evaluated via LC3 fluorescence intensity and Beclin-1 expression. Chloroquine (CQ), an autophagy inhibitor, was applied to further examine autophagy’s role. Conclusions: 5-HMF and isoverbascoside enhance autophagic activity in pancreatic β-cells, attenuate oxidative stress-induced apoptosis, and improve cell survival and proliferation. These findings underscore their potential as protective agents in T2DM by modulating the autophagy–apoptosis balance. Full article