Search Results (7,473)

Background and Objectives: The vedolizumab clinical decision support tool (VDZ-CDST) was developed to predict treatment outcomes in inflammatory bowel disease (IBD). While validated in clinical trial and consortium settings, its real-world performance remains less clear. The aim of our study was to evaluate the predictive value of pre-treatment CDST stratification for clinical and endoscopic outcomes and treatment persistence in real-world VDZ-treated IBD patients. Materials and Methods: We conducted a retrospective analysis of consecutive IBD patients initiating vedolizumab therapy, stratified by CDST risk groups. Clinical remission (CR) and corticosteroid-free remission (CSFR) at weeks 14 and 52 were assessed using PRO-2 in both Crohn’s disease (CD) and ulcerative colitis (UC). Endoscopic outcomes and treatment persistence were also evaluated. Results: 129 IBD patients, 57 with CD and 72 with UC, treated with vedolizumab were retrospectively stratified according to VDZ-CDST. In CD at week 52 the differences in CSFR between CDST groups were statistically significant (p = 0.04). A statistically significant association (p < 0.001) was also observed between CDST groups and endoscopic activity (EA) at follow-up endoscopy. In the low-probability group 69.2% showed persistent EA, whereas in the high-probability group 68.8% achieved endoscopic remission (ER). We also found significant differences (p = 0.004 and p < 0.001, respectively) in treatment persistence between CDST groups in CD. VDZ discontinuation rates were 76.9%, 28.6%, and 6.3% in the low-, intermediate-, and high-response groups, respectively. In UC, no predictive association was observed for either clinical or endoscopic outcomes nor treatment persistence; however, we observed relatively high remission rates despite CDST-based stratification. Conclusions: Although the VDZ-CDST failed to predict CR measured by PRO-2 in real-world IBD patients, it demonstrated meaningful associations with long-term CSFR, endoscopic outcomes and treatment persistence in Crohn’s disease. These findings support its role as a supportive tool in therapeutic decision-making, particularly when objective outcomes such as mucosal healing are prioritized. Prospective multicentre studies incorporating biomarkers and pharmacokinetic data are needed to refine VDZ-CDST for broader clinical application. Full article

Background: Long COVID presents a novel and emerging public health challenge. As the first point of contact, general practitioners (GPs) play a key role in diagnosing and coordinating the care of patients presenting with post-acute sequelae of COVID-19 (PASC), despite a lack of experience. This study aimed to identify the main difficulties encountered by GPs in Franche-Comté, France, in managing adult outpatients with long COVID. Methods: We conducted a cross-sectional survey using an anonymous online questionnaire, which contained 21 questions and was distributed to GPs in Franche-Comté, France. The survey assessed definition, diagnostic and therapeutic challenges in managing long COVID. Results: Among the 410 questionnaires distributed, 90 general practitioners (GPs) responded (response rate: 21.9%). The mean age of participants was 34 ± 10 years, and 64.4% were women (n = 58). Regarding knowledge of long COVID, three participants (3.3%) did not recognize it as a distinct clinical entity, while more than half (58.9%, n = 53) reported insufficient knowledge. The main challenges identified were therapeutic management (76.7%, n = 69) and diagnosis (75.6%, n = 68). Only 4.5% of respondents (n = 4) reported no difficulty in defining post-acute sequelae of SARS-CoV-2 infection (PASC). The most frequently reported diagnostic difficulty was distinguishing long COVID from differential diagnoses (93.3%, n = 83/89), particularly fibromyalgia (94.3%, n = 83/88). Only 37.1% of participants (n = 33/89) reported actively following up patients with PASC. During initial management, the main challenge was the difficulty in objectively assessing patients’ complaints using available diagnostic tools (80.7%, n = 67/83). Additionally, a large majority of GPs reported difficulties in addressing patients’ questions (86.7%, n = 72/83) and managing associated anxiety disorders (75.9%, n = 63/83). Conclusions: These findings highlight the immediate need to enhance GP training in Franche-Comté, France, in dealing with long COVID. Improvements such as harmonizing long COVID definitions, testing diagnoses, and strengthening interdisciplinary coordination are essential to provide coherent and patient-centered care for this disease. Full article

Therapeutic endoscopic ultrasound (t-EUS) has transformed the management of biliopancreatic diseases by enabling minimally invasive access and intervention through the gastrointestinal wall. This narrative review summarizes current indications and evolving roles of t-EUS in benign and malignant biliary disease, with a focus on the different modalities of transmural drainage, EUS-guided gastroenterostomy (EUS-GE), and EUS-guided radiofrequency ablation (EUS-RFA). In benign settings, EUS-gallbladder drainage (EUS-GBD) has emerged as a minimally invasive alternative to percutaneous cholecystostomy for high-risk patients with acute cholecystitis, offering internal drainage with fewer tube-related adverse events. In malignant biliary obstruction, transmural drainages are consolidated alternatives of endoscopic retrograde cholangiopancreatography (ERCP) as first-line or rescue strategies, providing durable internal biliary drainage, avoiding post-ERCP pancreatitis without deteriorating quality of life. In surgically altered anatomy, t-EUS overcomes the limitations of enteroscopy-assisted ERCP by creating direct access routes to the biliary tree or pancreatic duct. EUS-guided pancreatic duct drainage offers a rescue or primary approach in benign strictures, anastomotic stenosis, and disconnected duct syndrome. EUS-GE has rapidly become a preferred modality for palliation of gastric outlet obstruction in pancreatic cancer, while EUS-RFA provides a platform for locoregional therapy in selected cases of pancreatic neuroendocrine tumors, adenocarcinoma, and pancreatic cystic neoplasms. Collectively, these applications position t-EUS as a central tool in the multidisciplinary management of complex biliopancreatic disease, with ongoing innovations expected to further expand its indications and safety and to refine patient selection and training pathways. Full article

Background: Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder characterized by amyloid-β aggregation, tau hyperphosphorylation, oxidative stress, and mitochondrial dysfunction. Emerging evidence indicates that the gut microbiota plays a critical role in modulating neuroinflammatory, and metabolic pathways involved in AD pathogenesis through the microbiota-gut-brain axis. Objective: This systematic review aims to comprehensively evaluate the role of the microbiota-gut-brain axis in Alzheimer’s disease, with a particular focus on its mechanistic links to oxidative stress, mitochondrial dysfunction, and amyloid pathology, as well as its therapeutic potential. Methodology: A comprehensive literature search was conducted using PubMed, Scopus, and Web of Science databases, focusing on studies evaluating gut microbiota composition, metabolomic changes, oxidative stress markers, mitochondrial activity, and therapeutic interventions in AD models and patients. Results: Altered gut microbial composition in AD is associated with increased pro-inflammatory taxa (Escherichia-Shigella, Bacteroides) and depletion of short-chain fatty acid (SCFA) producing bacteria (Faecalibacterium, Roseburia). Dysbiosis contributes to systemic inflammation, disrupted intestinal permeability, and microglial activation, leading to oxidative damage and mitochondrial impairment in neurons. Preclinical and clinical studies indicate that probiotics, prebiotics, and fecal microbiota transplantation can restore redox balance, reduce neuroinflammation, and improve cognitive outcomes. Multi-omics and AI-based models are emerging as tools for identifying microbiome-derived biomarkers for early AD detection. Conclusion: The gut microbiota-mitochondria-oxidative stress axis represents a promising therapeutic target in Alzheimer’s disease. Future research should focus on longitudinal human studies, standardized microbial profiling, and personalized microbiome-based interventions to translate these mechanistic insights into clinical benefit. Full article

Background/Objectives: Blunt abdominal trauma is a frequent challenge in emergency medicine, but its diagnosis and treatment become significantly more complex when rare anatomical anomalies are present. Atypical anatomy may mask symptoms or mimic other acute abdominal conditions, causing delays in treatment. The aim of this paper is to review the literature on six rare anatomical anomalies and their impact on the consequences of blunt abdominal trauma. Methods: A Narrative literature review was undertaken, covering PubMed, Scopus, Web of Science and Google Scholar databases, analysing publications from 1960 to 2025. Case reports and case series (91 patients in total) with confirmed organ damage following blunt trauma in the course of: duodenal diverticulum, Meckel’s diverticulum, splenic torsion, rupture or torsion of the accessory spleen, visceral inversion (situs inversus) and horseshoe kidney. Results: Demographic analysis revealed a predominance of perforations of the duodenal diverticulum in older women (mean age 62 years), while younger men predominated in all other groups. The clinical picture was often non-specific or misleading, especially in situs inversus, where the location of pain did not correlate with the typical topography of organs. Contrast-enhanced computed tomography (CECT) has proved to be a key diagnostic tool, surpassing ultrasound/FAST scans due to its ability to provide precise anatomical imaging. Surgical treatment was predominant (100% in Meckel’s diverticulum, 95% in duodenal diverticulum), while conservative treatment was effective in horseshoe kidney injuries (94.8%). Mortality was highest in situs inversus (29%) and duodenal diverticulum perforation (20%). The vast majority of these fatal cases occurred in the era of modern computed tomography, suggesting that the therapeutic challenges stem directly from the specific nature of these anomalies, rather than from past diagnostic limitations. Conclusions: Anatomical anomalies significantly modulate the clinical manifestations of blunt abdominal trauma, increasing the risk of diagnostic errors. Early contrast-enhanced computed tomography and awareness of these rare pathologies are crucial for appropriate management and improved prognosis. Full article

Ocular infections and inflammation represent a clear risk to eye health, but standard eye masks often lack the necessary therapeutic features. Moreover, most existing studies employ a blended electrospinning approach, which leads to an inhomogeneous spatial distribution of the therapeutic agents. However, using the coaxial technique can address these limitations. This study develops a coaxial electrospun nanofibrous eye mask with dual antibacterial and antioxidant functions, aiming to provide an innovative ocular treatment tool for eye care. Generally, a core-shell structured bilayer polycaprolactone-polylysine/polyvinyl alcohol-resveratrol (PCL-PLs/PVA-RSV) membrane is successfully prepared by coaxial electrospinning, where the core is resveratrol-loaded PVA and the shell is PLs-loaded PCL. Results show uniform fiber morphology, favorable hydrophilicity, and potential for sustained release due to core-shell design. The membrane significantly inhibits the growth of Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli); at the same time, it exhibits excellent free radical scavenging ability and good component biocompatibility, achieving slow release of the two drugs and long-term antioxidant effect. This multifunctional platform offers a synergistic approach to combating microbial infection and oxidative stress, showing great potential for eye care. Full article

This manuscript presents an updated version of PEPlife, a manually curated database that provides extensive information on peptide half-life. The updated version, PEPlife2, contains 4500 total entries, including 2300 newly curated entries and 2200 entries from the previous PEPlife database. These entries correspond to 1673 unique peptide sequences and 257 unique protein sequences where different entries may refer to the same peptide/protein sequence, the half-life of which was evaluated using different experimental assays. Each entry contains detailed information, including experimental methods used to determine half-life, chemical modifications, biological activity, routes of administration, and other relevant data. In addition to unmodified peptide sequences, PEPlife2 includes cyclic peptides and chemically modified peptides, such as those with N- and C-terminal modifications. To provide structural insights, peptide and protein structures were sourced from the Protein Data Bank (PDB) or predicted using PEPstrMOD. PEPlife2 integrates advanced analytical tools including BLAST (version 2.7.1), Smith–Waterman and CLUSTALW. This database provides a valuable resource for peptide and protein therapeutics research, particularly in the design of immunotherapeutics and vaccines. Full article

Aging and obesity accompanied with hormonal disequilibrium represent critical, inter-related risk factors for breast cancer, significantly influencing disease incidence, progression, and therapeutic outcomes. This review aims to elucidate the multifaceted biological mechanisms linking obesity and aging to breast carcinogenesis, with a particular focus on the emerging therapeutic and preventive potential of postbiotics as molecules targeting cellular events important for cancer growth and responsiveness. Despite continuous advancement, breast cancer therapy still poses several challenges, such as treatment-induced acquired resistance, which is boosted by the inflammatory phenotype of senescent cancerous cells, as well as undesired side effects resulting from the destruction of normal cells. Such a complex background of breast carcinogenesis and oncotherapy resistance opens avenues to search for new preventive approaches and adjunctive treatment regimens. Postbiotics demonstrate a variety of benefits due to their selective antineoplastic activity, as well as the cytoprotective potential associated with antioxidant, anti-inflammatory and anti-senescent properties. Pleiotropic effects of postbiotics make them a promising tool for counteracting cellular and physiological disturbances that favor breast cancer development, including age- and obesity-related factors. They are prospective adjunctive agents in oncotherapy, albeit their efficacy and safety need to be thoroughly evaluated in clinical studies prior to implementation in routine treatment modes. Full article

The liver’s anatomic position and immune specialization make it both a major target and a major filter for systemically delivered therapeutics. Because portal venous inflow exposes the liver early to gut-derived molecules and exogenous compounds, many intravenously administered agents, including gene-based medicines and their viral and non-viral delivery systems, preferentially enter and accumulate in hepatic tissue. This review synthesizes how core liver physiology and immunobiology influence the performance, safety, and clinical translation of genomic medicines in hepatology, and outlines near-term practice and research shifts likely to define a genomics-driven future in liver disease care. We review the hepatic microarchitecture relevant to therapeutic trafficking, including sinusoidal transit, the space of Disse, hepatocyte uptake, and hepatobiliary elimination, and highlight the gatekeeping roles of liver sinusoidal endothelial cells and Kupffer cells in clearing particulate material and shaping inflammatory signaling. We then discuss how these same features create both opportunities, such as efficient hepatic targeting, and constraints, including innate immune activation, vector clearance, and variable intrahepatic distribution, for DNA- and RNA-based platforms. Finally, we propose five actionable developments poised to move genomics from a niche tool to a routine component of hepatology practice: earlier genomic testing in unexplained liver disease, multidisciplinary hepatology genome rounds, a centralized liver-specific gene resource, genetics-aware clinical trial design, and expansion of genetic therapies. Integrating liver biology with genomic medicine is essential to improve diagnostic yield, personalize therapy, and accelerate translation of gene-based treatments while mitigating immunologic and delivery-related barriers. Full article

Objectives: Platinum resistance remains a critical bottleneck in ovarian cancer management, yet reliable pre-treatment predictive tools are lacking. Existing markers like the platinum-free interval are retrospective, while genomic profiling is often cost-prohibitive. This study aimed to develop an accessible, machine learning-based dynamic weighted fusion (DWF) model using routine laboratory data to provide bidirectional risk stratification, particularly to reliably rule out platinum resistance before treatment initiation. Methods: In this retrospective study (2019–2023), seventy baseline clinical features were collected to differentiate platinum-resistant from platinum-sensitive ovarian cancer patients. We developed a DWF framework that dynamically integrates the top-performing classifiers from a library of 168 algorithms (combining 14 feature selection and 12 machine learning methods). Class imbalance was addressed via oversampling, and model efficacy was evaluated using area under the curve (AUC), accuracy, sensitivity, and specificity. Results: The DWF model achieved a robust AUC of 0.760 (95% CI: 0.683–0.837), outperforming all individual base classifiers. Subgroup analysis demonstrated highly consistent overall discrimination across initial treatment strategies (AUC of 0.755 for primary debulking surgery and 0.761 for neoadjuvant chemotherapy). Feature interpretation highlighted that resistance is driven by synergistic dysregulation of systemic inflammation and hypercoagulability, rather than single biomarkers. Conclusions: The proposed DWF model effectively leverages low-cost, standardized clinical data to serve as a robust bidirectional stratification tool. Its exceptional ability to rule out resistance provides clinicians with the evidence-based confidence to proceed with standard therapies, while its high-risk alerts identify candidates for early therapeutic adjustments and enhanced surveillance in ovarian cancer care. Full article

Background: Chronic Kidney Disease-associated Pruritus (CKD-aP) is a frequent, debilitating, and often underestimated symptom in clinical practice, with significant impacts on quality of life, sleep, mental health, and therapeutic adherence. This study aimed to develop a structured, person-centered nursing care overview for the management of CKD-aP. Methods: A comprehensive narrative review of the recent scientific literature on CKD-aP was conducted, adapting the conceptual domains of the European Specialist Nurses Organisation (ESNO) Common Training Framework (CTF) to nephrology nursing practice. The theoretical model guiding the work was Virginia Henderson’s paradigm, selected for its consistency with care models focused on promoting independence and meeting fundamental human needs. The study would answer the main research question “Which nursing evidence, tools, and strategies can support integrated, patient-centered management of CKD-aP?”. Results: A structured nursing care process was developed, articulated in sequential phases (assessment, problem definition, planning, intervention, and re-evaluation), visually represented in an operational flowchart and supported by validated clinical tools. The model emphasizes the nurse’s role in the multidimensional management of the symptom, incorporating educational, relational, therapeutic, and coordination-focused interventions. Conclusions: This proposal contributes to nephrology nursing practice by providing a theoretical and practical framework to standardize the management of CKD-aP. It promotes a holistic, evidence-based approach tailored to individual care needs, establishing a foundation for future clinical, educational, and research developments. Full article

Background/Objectives: Leishmaniasis is a group of diseases caused by obligate intracellular parasites of the Leishmania genus and is classified by the World Health Organization as a category I neglected tropical disease. Leishmania infantum predominantly affects children under five years of age and shows an increasing incidence of cutaneous and visceral forms. The development of new therapeutic alternatives remains challenging, making in silico approaches valuable for accelerating antileishmanial drug discovery. This study aimed to identify new compounds with potential activity against Leishmania infantum amastigotes using artificial intelligence-based classification models. Methods: A curated database of compounds with reported biological activity was constructed. Molecular representation employed zero- to two-dimensional descriptors calculated with Dragon software (v 7.0.10). Unsupervised k-means cluster analysis was applied to define training and external prediction sets. Supervised models were developed on the WEKA platform using IBk, J48, multilayer perceptron, and sequential minimal optimization algorithms. Model performance was assessed through internal cross-validation and external validation procedures. Results: All models achieved classification accuracies above eighty percent for both training and prediction sets, indicating consistent predictive performance and good generalization ability. The validated models were applied to virtual screening of the DrugBank database and a collection of synthetic compounds. This screening campaign enabled the identification of one hundred twenty compounds with potential activity against the amastigote form of Leishmania infantum. Conclusions: Artificial intelligence-based QSAR models proved to be useful tools for prioritizing antileishmanial candidates. The integration of molecular descriptors, machine learning, and virtual screening offers an efficient strategy for drug discovery. Full article

Scopolamine, also known as hyoscine, is a naturally occurring tropane alkaloid derived from plants of the Solanaceae family. Clinically, the compound has long been used for the prevention of motion sickness and postoperative nausea and vomiting, as well as for ophthalmological procedures requiring mydriasis and cycloplegia. However, beyond these established indications, increasing attention has been directed toward its broader neuropharmacological actions. This narrative review aims to summarise current knowledge regarding the pharmacological properties of scopolamine, with particular emphasis on its mechanisms of action and emerging implications in neuroscience and neuropsychiatric disorders. Scopolamine acts as a non-selective antagonist of muscarinic receptor subtypes M1–M5, interfering with cholinergic neurotransmission. Experimental and clinical studies demonstrate that scopolamine induces transient cognitive impairment. This property has led to its widespread use as a pharmacological model of Alzheimer’s disease, enabling investigation of cholinergic contributions to cognitive decline. More recently, several early clinical studies suggested that intravenous administration may produce rapid reductions in depressive symptoms, possibly through modulation of glutamatergic neurotransmission and activation of mTORC1-dependent synaptic plasticity pathways in the prefrontal cortex. Nevertheless, subsequent trials have yielded inconsistent results, and the therapeutic relevance of these findings remains uncertain. Current evidence indicates that scopolamine’s neuropsychiatric effects likely arise from complex interactions between cholinergic, glutamatergic, and neurotrophic signalling systems. Taken together, scopolamine represents both a valuable experimental tool for studying cholinergic function and a mechanistic framework for the development of novel therapeutics targeting rapid neuroplastic processes in neuropsychiatric disorders. Full article

The emergence of novel cytotoxic agents, multikinase inhibitors, and various antibody-based therapies has significantly expanded salvage therapy options for metastatic colorectal cancer (mCRC). Consequently, establishing the optimal treatment sequence for patients has become a formidable clinical challenge. Emerging evidence highlights the value of comprehensive biomarker assessment, particularly longitudinal monitoring of circulating tumor DNA (ctDNA), to capture dynamic molecular changes during treatment. Liquid biopsy-based technologies now enable real-time tracking of molecular alterations, supporting truly personalized therapeutic decision-making. Furthermore, prior treatment exposure and residual toxicities must be carefully considered to balance efficacy, safety, and quality of life. This review provides a comprehensive overview of the current salvage-line landscape for mCRC, discusses the clinical utility of ctDNA as a predictive and prognostic tool, and proposes integrated strategies to optimize therapeutic outcomes in the evolving era of precision medicine. Full article

Extensive evidence now confirms Lipoprotein(a) [Lp(a)] as a causal, independent risk factor for atherosclerotic cardiovascular disease. Elevated Lp(a) levels are detected in approximately 20% of the global population, positioning it as a major contributor to residual cardiovascular risk. Circulating Lp(a) levels are determined predominantly by genetic factors, so they are largely unresponsive to lifestyle modifications or conventional lipid-lowering therapies. Therefore, multiple international guidelines now endorse a one-time, lifetime measurement of Lp(a), as lowering Lp(a) concentrations is expected to have a positive impact on the reduction of cardiovascular risk. Currently, the therapeutic landscape of Lp(a) lowering drugs is rapidly evolving. Some RNA-based therapies (antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs)) have been demonstrated to reduce plasma Lp(a) concentrations by up to 98% in early-phase clinical trials. The efficacy and safety of these compounds are currently being evaluated in large-scale cardiovascular outcome trials. The results of these studies will be critical in validating the “Lp(a) hypothesis”: specific reduction of Lp(a) levels can lead to a measurable decrease in cardiovascular events. The purpose of this narrative review is to examine and discuss the available evidence on the role of Lp(a) as a risk factor and pharmacological target to provide a practical tool for decision-making in clinical practice. Full article