Search Results (8,866)

Background/Objectives: Older individuals are more vulnerable to stress and trauma. Although pressure injuries (PIs) are recognized as a significant complication, the specific impact of frailty on PI development in older Asian trauma patients remains insufficiently explored. This study aims to investigate the factors associated with the occurrence of hospital-acquired pressure injuries (HAPU) in older patients aged ≥65 years, including frailty. Methods: This study is a retrospective secondary data analysis of 3418 older trauma patients admitted to a regional trauma center (including ICU and trauma ward) from 1 January 2020 to 31 December 2023. Patients with PIs present on admission (POA) were excluded to strictly analyze new PI occurrence. Frailty was assessed using the mFI-5. Results: The mean age of participants was 77.33 years. During hospitalization, 2.5% (n = 84) of patients developed new PIs. Multivariate logistic regression identified that higher frailty score (Odds Ratio [OR] = 1.59, 95% Confidence Interval [CI]: 1.26–2.02), lower BMI (OR = 0.93, 95% CI: 0.86–0.99), hypoalbuminemia (OR = 0.55, 95% CI: 0.36–0.84), and prolonged hospital stay (OR = 1.05, 95% CI: 1.04–1.06) were independently associated with PI occurrence. Chronological age was not a significant predictor in the multivariate model. Conclusions: Frailty, nutritional status (BMI, albumin), and prolonged hospital stay are significant factors associated with HAPU in older trauma patients. Full article

Structural valve deterioration (SVD) remains a key limitation in bioprosthetic heart valve (BHV) usage influenced by patient age. A deeper understanding of SVD pathogenesis, particularly of the immune-mediated processes altering current BHV materials, is therefore critical. To this end, commercially available BHV tissues of bovine, porcine, and equine origin were investigated following subcutaneous implantation into α1,3-galactosyltransferase-knockout (Gal KO) mice. We compared the immune responses between adult and aged animals via histological assessments of explants and measurement of serum anti-galactose α1,3-galactose (Gal) and anti-non-Gal antibodies at 2 months post-implantation. In contrast to adult mice, old Gal KO mice did not show increased levels of serum anti-Gal or -non-Gal antibodies after receiving specific BHV tissue (i.e., Freedom-Solo). Instead, a significant decrease in serum anti-Gal IgM was found in old recipients of Freedom-Solo. Furthermore, the overall cellular immune response was attenuated in explants from old mice compared with adults (i.e., ATS 3f and Crown). Nevertheless, the Freedom-Solo (bovine) and the Hancock-II (porcine) tissues still elicited strong cellular immune infiltration in the old cohorts. Therefore, the Gal KO mouse model offers a valuable platform to investigate age-related differences regarding cellular and humoral immune responses to various BHV tissues, contributing to our understanding of SVD. Full article

KCNV2 encodes Kv8.2, an electrically silent voltage-gated potassium channel subunit that is expressed in photoreceptors. Disease-causing variants in KCNV2 cause a monogenic disorder which is classified clinically as cone dystrophy with supernormal rod response (CDSRR). Here, we generated KCNV2-deficient human retinal organoids as a tool for gene therapy vector potency assessment. The organoids were derived from two separate sources: by generating IPSCs from patient blood and by gene editing of a control cell line. Eight KCNV2 gene therapy vectors were assessed in retinal organoids; Kv8.2 protein levels and its in situ interactions with potassium channel binding partners were quantitatively assessed. We show significant enhancements in vector potency and specificity by transgene codon optimisation and the use of the photoreceptor-specific rhodopsin kinase (RK) promoter, respectively. Single-cell RNA sequencing was performed in transduced retinal organoids to assess the performance of the AAV vectors at single-cell resolution. KCNV2-deficient photoreceptors had an upregulation in genes associated with apoptosis, oxidative stress, and hypoxia pathways which were partially restored in AAV-KCNV2 transduced photoreceptors. These data show how human retinal organoids can be used to evaluate AAV gene therapy vector potency in vitro in a physiologically relevant model for the selection of lead therapeutic candidates and to help minimise the use of animals in preclinical development. Full article

The accurate determination and quantification of praziquantel are essential for optimizing its therapeutic effectiveness in treating schistosomiasis and neurocysticercosis, two significantly neglected tropical diseases. Its challenging physicochemical profile, extensive metabolism, and stereochemical complexity requires robust analytical methods for reliable quantification in clinical, veterinary, and pharmaceutical samples. This review provides a comprehensive and critical evaluation of analytical strategies used for PZQ determination, spanning fluorometric and radiometric assays, HPLC–UV, LC–MS, LC–MS/MS, and enantioselective chromatographic approaches. Particular emphasis is placed on the evolution toward highly sensitive LC–MS/MS methods and their alignment with contemporary regulatory expectations, including ICH M10 requirements. These advancements have significantly improved sensitivity, specificity, and reproducibility, which are crucial for pharmacokinetic, pharmacodynamic, and bioequivalence studies. Enantioselective methods for distinguishing PZQ enantiomers and metabolites are discussed. The aim of these innovations is to increase praziquantel bioavailability, improve patient adherence, and support its continued use in mass drug administration programs. Finally, the review highlights implementation challenges in resource-limited settings and proposes analytical models to expand global bioanalytical capacity. Together, these insights provide a structured foundation for selecting and developing high-quality, regulatory-compliant analytical methods for PZQ. Full article

The surge in demand for patient-specific orthopedic implants necessitates the precise optimization of design and processing parameters for artificial trabecular bone. This research utilizes Voronoi-based porous structures to replicate the irregular geometry characteristic of natural trabecular bone. All specimens were fabricated through fused deposition modeling (FDM) with polylactic acid (PLA). The study systematically investigated the influence of four primary parameters, namely build orientation, extruder temperature, layer height, and pore count, on compressive strength. To ensure experimental efficiency, the research implemented a Taguchi L20 orthogonal array. Subsequent signal-to-noise (S/N) ratio analysis identified the optimal parameter set as a y-90° build orientation, an extruder temperature of 200 °C, a layer height of 0.2 mm, and a count of 150 pores. These findings underscore the necessity of integrated geometric and process parameter optimization to advance additive manufacturing for orthopedic applications. Full article

(1) Background: The transcription factor p73 exists in multiple isoforms with divergent functions in cancer. While DNp73 promotes stemness, epithelial–mesenchymal transition (EMT), and metastasis, the tumor-suppressive isoform TAp73 can also switch to promoting cancer progression. How isoforms sharing the same DNA-binding domain produce divergent outcomes remains unclear. (2) Methods: Here, we performed CUT&RUN in combination with JASPAR, transcriptomics, proteomics, patient survival and gene expression data to map genome-wide and promoter-associated DNA-binding and coregulatory transcription factor (coTF) profiles of TAp73α and DNp73β in melanoma cells. (3) Results: Systematic screening for motif enrichment in cancer hallmark gene sets revealed TAp73- and DNp73-specific coTF repertoires with distinct functions. We identified a coregulator signature for EMT genes enriched for both isoforms that has tumor context-dependent effects on survival and correlates with unfavorable patient prognosis. Of these EMT-associated coTFs, PATZ1 was validated as a novel direct interactor of DNp73β. (4) Conclusions: Our results provide a comprehensive reference map of p73 isoform-specific binding and coregulator recruitment and establish a workflow to model their influence on cancer reprogramming with implications for AI-based individualized therapy. Full article

Background: Immune checkpoint inhibitors (ICIs) are a new anti-cancer therapy that have improved survival rates in many aggressive cancers. However, while rare, a significant number of patients develop ICI-induced cardiotoxicity. Clinical manifestations are non-specific and underlying cellular mechanisms remain unknown, making diagnosis and treatment of these ICI-induced cardiac side effects difficult. Exercise has shown protective effects against chemotherapy-induced cardiotoxicity but has not been investigated in combination with ICIs. High-intensity exercise has shown greatest cardioprotective effects in preclinical (animal) models, but human cancer patients prefer low-intensity exercise in the clinical setting. Therefore, the purpose of this study was to further identify the cardioprotective effects of low-intensity exercise as a treatment strategy against ICI-induced cardiotoxicity. Methods: Female mice were randomly selected and separated into four groups: sedentary (SED), sedentary ICI-treated (SED + ICI), low-intensity treadmill-exercised (TM), and low-intensity treadmill-exercised ICI-treated mice (TM + ICI). Mice either underwent a 4-week low-intensity treadmill exercise protocol (TM) or remained sedentary (SED). During the 4 weeks, ICI mice received anti-PD-1 treatment (200 μg/mouse) via intraperitoneal injections twice each week. Echocardiography was performed at baseline and sacrifice to determine changes in cardiac structure and function. At sacrifice, cardiac tissue was collected, weighed, and frozen for further biochemical analysis. Underlying metabolic signaling pathways were assessed via Western Blot, and autophagic flux was analyzed via fluorescent microscopy. Results: Echocardiography at sacrifice revealed significantly decreased fractional shortening as a measure of cardiac function (−20%), 1.5-fold dilation of the left ventricle, and thinning of the posterior cardiac wall at systole and diastole in SED + ICI mice compared to SED controls (p < 0.05), indicative of a phenotype of ICI-induced dilated cardiomyopathy. TM + ICI mice did not show a significant difference in these cardiac structural and functional parameters, suggesting cardioprotective effects of low-intensity exercise. In line with these findings, Western Blot and fluorescent microscopy analyses revealed upregulation of autophagic flux (p < 0.05), as well as dysfunctional metabolic pathways (p < 0.05) in ICI-treated mice compared to non-ICI controls. Low-intensity exercise was associated with regulation of dysfunctional metabolism and autophagy in TM + ICI compared to SED + ICI mice. Conclusions: The clinically relevant ICI treatment protocol used in this study led to significant cardiac dysfunction and remodeling, accompanied by underlying dysfunctional metabolism and autophagy. Low-intensity exercise was capable of regulating abnormal protein synthesis and degradation and protecting against ICI-induced cardiotoxicity. This study adds knowledge to the characterization of still unclear clinical manifestations of ICI-induced cardiotoxicity, underlying signaling pathways that could shed light on potential pharmacological treatment targets, as well as the protective effects of low-intensity exercise as a non-pharmacological treatment strategy. Full article

Introduction: Prompt diagnosis and differentiation between non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC) are essential in the treatment of bladder cancer. Inflammation-based biomarkers have recently emerged as potential tools for improving cancer diagnostics and prognostication. This study aims to evaluate the potential value of the Systemic Inflammation Index (SII), Systemic Inflammation Response Index (SIRI), Pan-immune Inflammation Value (PIV), and Platelet-to-Lymphocyte Ratio (PLR) as predictors of muscle-invasive disease. Materials and methods: Analyzed data included 310 bladder tumors. The SII, SIRI, PIV, and PLR were calculated from pre-TURBT complete blood-count results. Differences in inflammatory markers between pathological stages (pTa–pT4) were examined using ANOVA with Tukey’s post hoc testing. Optimal cutoff values for distinguishing NMIBC from MIBC were identified using ROC curve analysis and Youden’s J statistic. Logistic regression models incorporating age, sex, the number of recurrences, and each inflammatory index were developed to evaluate their predictive performance in patients treated with curative intent. Results: All investigated inflammation indices significantly differed across tumor stages (p < 0.001), with lower values observed in pTa tumors compared with muscle-invasive disease. Determined cutoff values for muscle-invasive disease were 865.63 for SII, 2.02 for SIRI, 579.28 for PIV, and 166.35 for PLR. Logistic regression models demonstrated promising diagnostic performance, achieving AUC values of 0.812 (SII), 0.816 (SIRI), 0.821 (PIV), and 0.795 (PLR); sensitivity and specificity were 76% and 75% for SII, 79% and 77% for SIRI, 80% and 72% for PIV, and 88% and 59% for PLR. Discussion: The presented results indicate that inflammation-based indices vary meaningfully between bladder cancer stages and may be utilized in early identification of muscle-invasive disease. As inexpensive and widely available biomarkers, they offer potential value in the evaluation of suspected MIBC before the final pathology report and could enhance the diagnostic process. Full article

Background: Pediatric craniocervical junction (CCJ) anomalies consist of a unique subset of anatomically complex spine conditions. The aims of intervention are to achieve long-term stability, correct existing deformity, and prevent neurological compromise. However, surgery is challenging due to critical neurovascular and musculoskeletal structures in the limited operative space of a young child. Recently, the use of three-dimensional (3D) printed models has been demonstrated to be valuable neurosurgical adjuncts. We therein report the application of a 3D-printed model for a pediatric case with a complex CCJ condition. A systematic review of the related literature is concurrently performed. Case description: A 10-year-old male presented with torticollis associated with neck pain and progressive thoracic kyphosis. Neuroimaging reported an unfused os odontoideum inferior to the basion and anterior half of the C2 vertebral body and anteriorly angulated with the C1 anterior arch. Of note, there was a large vertebral vein coursing over the left C2 lamina that was predominantly draining into the CCJ venous plexus. A radiologically derived 3D model of the patient’s CCJ was printed and used for pre-operative planning, multi-disciplinary team discussion, and detailed counseling with the patient and caregivers. The patient underwent an uneventful C1–C2 posterior screw fixation and has recovered well since. Separately, we observed there is a paucity of publications specific to this topic. Conclusions: As demonstrated, a custom-made 3D model was useful for clinicians work through technical difficulties and improve the perioperative discussion process in an otherwise difficult case. Full article

Background: Vaccinations are essential to protect travelers from infectious diseases, especially in high-risk destinations. However, awareness and adherence to vaccination recommendations vary, influenced by communication, personal beliefs, and behavior. Methods: A focus group was conducted in February 2025 at a local health authority in central Italy, specifically within its travel clinic, to explore travelers’ awareness, attitudes, and behaviors regarding vaccination. The discussion was analyzed using the “3Cs” Vaccine Hesitancy model. Participants were purposively selected to ensure diversity and representativeness. Discussions included past travel experiences, knowledge of required vaccines, motivations for immunization, and barriers to access. Results: Four key thematic areas emerged: socio-cultural/environmental factors, psychological/emotional influences, knowledge/information access, and general health perceptions. Communication gaps often weakened belief in vaccine efficacy and necessity. Cultural background, past experiences, and risk perception heavily influenced decisions. Discussion: Although vaccination is widely viewed as a protective measure, vaccine hesitancy persists due to misinformation and limited institutional trust. The COVID-19 pandemic intensified both awareness and skepticism. The 3Cs model clarified hesitancy levels and barriers, emphasizing the need for effective communication and trust-building. Conclusions: Enhancing access to accurate information, strengthening healthcare professionals’ communicative role, and reducing economic obstacles are crucial. Tailored awareness campaigns and integrated health policies are essential to increasing vaccine uptake, safeguarding traveler health, and limiting global disease spread. Patient or Public Contribution: Members of the public contributed to this study by participating in a focus group, where they shared their personal experiences, perceptions, and opinions regarding travel-related vaccinations. Their insights provided valuable qualitative data that helped inform the study’s findings. However, they were not involved in the study design, the analysis of the data, or the preparation of the manuscript. The role of participants was limited to the data collection phase of the study. Full article

Background/Objectives: Small bowel obstruction (SBO) is a common surgical emergency associated with significant morbidity and mortality. This retrospective analysis aimed to identify key predictors for the need for surgery in SBO management and to develop a simple clinical risk score to support decision-making. Methods: This retrospective study included 285 patients treated for SBO at the University Hospital Erlangen from 2018 to 2022. Pretherapeutic clinical, laboratory, and imaging data, as well as treatment details and outcome parameters were assessed and analyzed using univariate and multivariate logistic regression to identify significant predictors for the need of surgery. A weighted point-based risk score was then derived from the final model, and its discriminative performance was evaluated using receiver operating characteristic (ROC) analysis. Results: Of the 285 patients, 234 (82.1%) underwent surgery and 51 (17.9%) were successfully managed conservatively. Multivariate analysis identified the following independent predictors for surgery: 0–1 previous abdominal operation (OR 4.7, p = 0.009), serum albumin ≤ 34 g/L (OR 4.5, p = 0.011), free intraperitoneal fluid on imaging (OR 3.6, p = 0.015), air–fluid levels on plain abdominal X-ray (OR 3.5, p = 0.024) and a transition point on CT (OR 11.4, p = 0.002). A weighted score (range 0–6 points) was constructed, assigning 1 point to each of the first four predictors and 2 points to the transition point. The score showed good discrimination for predicting the need for surgery (AUC 0.874). Using a cut-off of ≥3 points, sensitivity was 96.2% and specificity 64.7%. The observed proportion of patients requiring surgery increased from 21.4% in the low-risk group (0–2 points) to 88.6% in the intermediate-risk group (3–4 points) and 97.3% in the high-risk group (5–6 points). Conclusions: The proposed predictors and the weighted risk score may support bedside decision-making in SBO by distinguishing patients who require surgery from those eligible for conservative management, but they require prospective multicenter validation before routine clinical implementation. Full article

Background: Total hip arthroplasty (THA) is a well-tolerated and effective procedure that can improve a patient’s mobility and quality of life. A main concern, however, is the release of metal ions into the body due to wear and corrosion. Commonly reported ions are Co and Cr, while others, such as Ti, Mo, and Ni, are less frequently studied. The objective of this study was to characterize compartmentalization and time-dependent ion behaviors across serum, whole blood, and urine after hip prosthetic implantation. The goal of using Random Forest (RF) was to determine whether machine learning modeling could support temporal trends across data. Methods: Data was gathered from the literature of clinical studies, and we conducted a pooled analysis of the temporal kinetics from cohorts of patients who received hip prosthetics. Mean ion concentrations were normalized to µg/L across each fluid and weighted by cohort sample size. RF was used as a study-level test of predictive accuracy across ions. Results: For serum and whole blood, Co and Cr displayed one-phase association models, while Ti showed an exponential rise and decay. Ions typically rose quickly within the first 24 months postoperatively. Serum Co and whole blood had similar patterns, tapering off just under 2 µg/L, but serum Cr (~2.02 µg/L) was generally higher than that of whole blood (~0.99 µg/L). Mean urinary Co levels were greater than those of Cr, suggesting a larger, freely filterable fraction for Co. RF was implemented to determine predictive accuracy for each ion, showing a stronger fit for Co (R² = 0.86, RMSE = 0.57) compared to Cr (R² = 0.52, RMSE = 0.50). Conclusions: Sub-threshold exposure was prevalent across cohorts. Serum and whole blood Co and Cr displayed distinct kinetic profiles and, if validated, could support fluid-specific monitoring strategies. We present a methodology for interpreting ion kinetics and show potential for machine learning applications in postoperative monitoring. Full article

Total hip arthroplasty (THA) is a transformative procedure for managing severe hip disorders, yet implant longevity remains a critical challenge, particularly for younger, active patients. Wear-related complications are a leading cause of revision surgery, emphasizing the need for optimized design and material performance. This systematic review aims to synthesize evidence on the wear behavior, material properties, and design parameters of hip implants with a focus on finite element analysis (FEA)-based predictive approaches. A comprehensive literature search was conducted across Scopus, PubMed, ScienceDirect, MDPI, and Cochrane databases following PRISMA guidelines. Studies published between 2010 and 2025 were included if they addressed THA biomechanics, wear analysis, or material optimization using FEA, hip simulators, or radiostereometric techniques. Key findings reveal that larger femoral heads, while reducing contact pressure, increase wear due to greater sliding distance. Gravimetric wear rates ranged from 3.15 ± 0.27 mg/Mc to 2.18 ± 0.31 mg/Mc, while linear and volumetric wear reached 0.0375 mm/Mc and 33.6 mm³/Mc, respectively. Stress analysis showed custom stems exhibited markedly lower von Mises stress (194.9 MPa) compared to standard designs (664.3 MPa), and fatigue assessments confirmed a factor of safety > 1 across profiles. Patient-specific factors, such as body weight, significantly influenced wear with a 26% increase in metal wear observed between 100 kg and 140 kg. This systematic review synthesizes current research on total hip arthroplasty, emphasizing biomechanical and material factors critical for implant longevity and patient care. It uniquely integrates FEA-based wear prediction with clinical implications, bridging computational modeling, geometry optimization, and material performance to provide actionable insights for next-generation, patient-specific hip implant design. Full article

Severe dengue virus (DENV) infections are associated with circulating non-neutralizing antibodies generated during heterotypic infections. Although antibodies are key mediators of both protection and pathogenesis, the specific dynamics of B cells (Bc) and their antibody responses remain insufficiently characterized due to limited methods of identifying DENV-specific Bc (DENV-Bc) and the absence of animal models resembling the human disease. Here, we developed a spectral flow cytometry assay employing biotinylated virus-like particles (VLPs) to detect DENV-Bc in C57BL/6 mice and children hospitalized with dengue. DENV-1 and DENV-2 VLPs were biotinylated, and the efficiency of biotin incorporation was assessed with an HABA-avidin assay and ELISA. Serotype specificity and optimal binding conditions were confirmed using hybridomas 4G2 (pan-flavivirus) and 3H5-1 (DENV-2 specific). Fluorescent agglutimers were subsequently generated by coupling biotinylated VLPs to streptavidin–fluorochrome complexes. Splenocytes from intraperitoneally DENV-infected mice and peripheral blood mononuclear cells (PBMCs) from naturally infected pediatric patients were stained with these VLPs and Bc-lineage markers. Biotinylated VLPs bound specifically to hybridomas, and this binding was competitively inhibited by unlabeled VLPs. After secondary DENV challenge, VLPs identified DENV-specific class-switched plasmablasts in mice. Circulating DENV-specific plasmablasts were also detected in children, with agglutimers enabling the discrimination of serotype-specific and cross-reactive responses in primary and secondary infections. This VLP-based approach represents a scalable platform to investigate the protective and pathogenic roles of DENV-Bc in infection and vaccination. Full article

Background: Dyspepsia is a common indication for gastroscopy, yet its diagnostic yield for malignancy and other clinically significant findings (CSF) remains low. Improved risk stratification is therefore essential to guide endoscopic referral. This study evaluates the diagnostic yield of gastroscopy in dyspepsia and investigates the predictive roles of age, ethnicity, and alarm symptoms. Methods: This retrospective single-center study was conducted at a university-affiliated hospital in Israel and included 3022 patients who underwent gastroscopy for dyspepsia over a five-year period. Multivariate logistic regression identified independent predictors of CSF, and receiver operating characteristic (ROC) analysis determined optimal age thresholds for malignancy and CSF. Results: Functional dyspepsia accounted for 55.9% of cases, while precancerous gastric lesions and upper gastrointestinal malignancies were identified in 12.8% and 0.79%, respectively. In multivariable models, age ≥ 50 years (OR = 2.59; CI: 2.02–3.32) and alarm symptoms (OR = 1.79; 95% CI: 1.33–2.41) independently predicted CSFs. Malignancy was similarly associated with age ≥ 50 years (OR = 4.89; CI: 1.11–21.60) and alarm symptoms (OR = 31.42; CI: 10.26–96.19). ROC analysis identified optimal age thresholds of 50 years for CSF (AUC = 0.65) and 54 years for malignancy (AUC = 0.72). Ethnicity did not independently predict malignancy, though minority patients showed differing precancerous lesion patterns. Conclusions: Age ≥ 50 years and alarm symptoms significantly increased the likelihood of CSFs and malignancy, supporting a selective approach to gastroscopy. ROC-derived thresholds may support reconsideration of age criteria in settings with similar epidemiologic patterns, highlighting the need for region-specific risk stratification. Full article