Search Results (28,357)

The epidermal growth factor receptor (EGFR) is a key target for both cancer diagnosis and therapeutic interventions. Assessing EGFR expression before therapy has become routine in clinical practice, yet current methods like biopsy and immunohistochemistry (IHC) have significant limitations, including invasiveness, limited repeatability, and lack of real-time, whole-body data. EGFR-targeted imaging has emerged as a promising alternative. EGFR-targeting peptides, owing to their favorable physicochemical properties and versatility, are increasingly being explored for a variety of applications, including molecular imaging, drug delivery, and targeted therapy. Recent advances have demonstrated the potential of EGFR-targeting peptides conjugated to imaging probes for non-invasive, real-time in vivo tumor detection, precision therapy, and surgical guidance. Here, we provide a comprehensive overview of the latest progress in EGFR-targeting peptides development, with a particular focus on their application in the development of molecular imaging agents, including fluorescence imaging, PET/CT, magnetic resonance imaging, and multimodal imaging. Furthermore, we examine the challenges and future directions concerning the development and clinical application of EGFR-targeting peptide-based imaging probes. Finally, we highlight emerging technologies such as artificial intelligence, mutation-specific peptides, and multimodal imaging platforms, which offer significant potential for advancing the diagnosis and treatment of EGFR-targeted cancers. Full article

Introduction: The combination of ceftazidime−avibactam (CAZ-AVI) with aztreonam (ATM) may be an option for the treatment of infections due to metallo-β-lactamases (MBLs) producing bacteria, as recommended by current guidelines. MBLs protect the pathogen from any available β-lactam/β-lactamase inhibitor (BL/BLI). Moreover, in vitro and clinical data suggest that double carbapenem therapy (DCT) may be an option for such infections. Materials and Methods: This retrospective study was conducted in two mixed intensive care units (ICUs) at the University Hospital of Larissa, Thessaly, Greece, and the General Hospital of Larissa, Thessaly, Greece, during a three-year period (2022−2024). Mechanically ventilated patients with bloodstream infection (BSI) caused by K. pneumoniae resistant to all BL/BLI combinations were studied. Patients were divided into three groups: in the first, patients were treated with CAZ-AVI + ATM; in the second, with DCT; and in the third, with antibiotics other than BL/BLIs that presented in vitro susceptibility. The primary outcome of the study was the change in Sequential Organ Failure Assessment (SOFA) score between the onset of infection and the fourth day of antibiotic treatment. Secondary outcomes were SOFA score evolution during the treatment period, total duration of mechanical ventilation (MV), ICU length of stay (LOS), and ICU mortality. Results: A total of 95 patients were recruited. Among them, 23 patients received CAZ-AVI + AZT, 22 received DCT, and 50 patients received another antibiotic regimen which was in vitro active against the pathogen. The baseline characteristics were similar. The mean (SE) overall age was 63.2 (1.3) years. Mean (SE) Acute Physiology and Chronic Health Evaluation II (APACHE II) and SOFA scores were 16.3 (0.6) and 7.6 (0.3), respectively. The Charlson Index was similar between groups. The control group presented a statistically lower SOFA score on day 4 compared to the other two groups [mean (SE) 8.9 (1) vs. 7.4 (0.9) vs. 6.4 (0.5) for CAZ-AVI + ATM, DCT and control group, respectively (p = 0.045)]. The duration of mechanical ventilation, ICU LOS, and mortality were similar between the groups (p > 0.05). Comparison between survivors and non-survivors revealed that survivors had a lower SOFA score on the day of BSI, higher PaO₂/FiO₂ ratio, higher platelet counts, and lower lactate levels (p < 0.05). Septic shock was more frequent among non-survivors (60.3%) in comparison to survivors (27%) (p = 0.0015). Independent factors for mortality were PaO₂/FiO₂ ratio and lactate levels (p < 0.05). None of the antibiotic regimens received by the patients was independently associated with survival. Conclusions: Treatment with CAZ-AVI + ATM or DCT may offer similar clinical outcomes for patients suffering from BSI caused by K. pneumoniae strains resistant to all available BL/BLIs. However, larger studies are required to confirm the findings. Full article

Background/Objectives: This study aims to evaluate the additional value of [¹⁸F]F-fluorocholine ([¹⁸F]F-FCH) PET/CT over contrast-enhanced magnetic resonance imaging (CE-MRI) in detecting the recurrence of brain metastases (BMs) after stereotactic radiosurgery (SRS) in patients with lung cancer brain metastases (LCBMs). Methods: Thirty-one patients with suspected recurrence of BM in LCBM after SRS were enrolled in this retrospective study. They underwent both [¹⁸F]F-FCH PET/CT and CE-MRI within 2 weeks. The tumor imaging parameters and clinical features were analyzed. The results of histopathology or radiographic follow-up served as the reference standard for the final diagnosis. Results: In these 31 patients, there were 54 lesions, of which 27 lesions were proven to be BM recurrence, while 27 lesions were non-recurrence. [¹⁸F]F-FCH PET/CT showed high radiotracer uptake in recurrent lesions of BM and identified 24 positive lesions (88.89% of sensitivity), while CE-MRI indicated 23 positive lesions (85.19% of sensitivity). [¹⁸F]F-FCH PET/CT indicated higher specificity (81.48%) and accuracy (85.19%) in detecting recurrence of BM than CE-MRI (40.74% and 62.96%, both p < 0.05), particularly in frontal lobes and cerebella. For lesion sizes, the accuracy of [¹⁸F]F-FCH PET/CT in detecting recurrent lesions was higher than that of CE-MRI for lesions over 1.0 cm but below 2.0 cm (p = 0.016). The detective performance of [¹⁸F]F-FCH PET/CT combined with CE-MRI was higher than [¹⁸F]F-FCH PET/CT or CE-MRI alone (all p < 0.05). Interestingly, TLC (≥4.11) was significantly correlated with poor intracranial PFS (iPFS), meaning it was a significant prognostic factor for iPFS. Conclusions: This study identified that compared with CE-MRI, [¹⁸F]F-FCH PET/CT demonstrated higher specificity and accuracy in diagnosing recurrence of BM in LCBM after SRS. Combining [¹⁸F]F-FCH PET/CT with CE-MRI has the potential to improve diagnostic performance for recurrence of BM and management of patient treatment. TLC was an independent risk factor for iPFS. Full article

The efficacy of botulinum toxin A (BoNT) in alleviating motor symptoms of cervical dystonia (CD) has been well established, and it is the treatment of choice in this disease. Lately, the effect of BoNT on non-motor symptoms (NMS) such as cognitive function, depression, anxiety, pain, and sleep disturbance has been observed in patients with CD. A comprehensive clinical and functional assessment of motor (dystonia severity, gait) and non-motor symptoms (cognitive functions, depression, anxiety, sleep, and pain) has been performed in a total of 34 adult patients with cervical dystonia before and after BoNT treatment. Results have also been compared to a control group. Significant improvements in the scales assessing dystonia severity have been observed, which is in line with previous studies on the effect of BoNT on motor symptoms in dystonia. Interestingly, the results also clearly indicate that BoNT has a positive effect on NMS. Among the studied non-motor domains, depression and cognitive functions improved the most after the treatment procedure. The study highlights the potential of BoNT to positively influence non-motor symptoms in patients with cervical dystonia, although its effect on various NMS is not equal. Full article

Pediatric asthma is a multifactorial and heterogeneous disease determined by the dynamic interplay of genetic susceptibility, environmental exposures, and immune dysregulation. Recent advances have highlighted the pivotal role of epigenetic mechanisms, in particular, DNA methylation, histone modifications, and non-coding RNAs, in the regulation of inflammatory pathways contributing to asthma phenotypes and endotypes. This review examines the role of respiratory viruses such as respiratory syncytial virus (RSV), rhinovirus (RV), and other bacterial and fungal infections that are mediators of infection-induced epithelial inflammation that drive epithelial homeostatic imbalance and induce persistent epigenetic alterations. These alterations lead to immune dysregulation, remodeling of the airways, and resistance to corticosteroids. A focused analysis of T2-high and T2-low asthma endotypes highlights unique epigenetic landscapes directing cytokines and cellular recruitment and thereby supports phenotype-specific aspects of disease pathogenesis. Additionally, this review also considers the role of miRNAs in the control of post-transcriptional networks that are pivotal in asthma exacerbation and the severity of the disease. We discuss novel and emerging epigenetic therapies, such as DNA methyltransferase inhibitors, histone deacetylase inhibitors, miRNA-based treatments, and immunomodulatory probiotics, that are in preclinical or early clinical development and may support precision medicine in asthma. Collectively, the current findings highlight the translational relevance of including pathogen-related biomarkers and epigenomic data for stratifying pediatric asthma patients and for the personalization of therapeutic regimens. Epigenetic dysregulation has emerged as a novel and potentially transformative approach for mitigating chronic inflammation and long-term morbidity in children with asthma. Full article

Prostate cancer (PC) remains a leading cause of malignancy in men worldwide, with current diagnostic methods such as prostate-specific antigen (PSA) testing and tissue biopsies facing limitations in specificity, invasiveness, and ability to capture tumor heterogeneity. Liquid biopsy, especially analysis of circulating tumor DNA (ctDNA), has emerged as a transformative tool for non-invasive detection, real-time monitoring, and treatment selection for PC. This review examines the role of ctDNA in both localized and metastatic PCs, focusing on its utility in early detection, risk stratification, therapy selection, and post-treatment monitoring. In localized PC, ctDNA-based biomarkers, including ctDNA fraction, methylation patterns, fragmentation profiles, and mutations, demonstrate promise in improving diagnostic accuracy and predicting disease recurrence. For metastatic PC, ctDNA analysis provides insights into tumor burden, genomic alterations, and resistance mechanisms, enabling immediate assessment of treatment response and guiding therapeutic decisions. Despite challenges such as the low ctDNA abundance in early-stage disease and the need for standardized protocols, advances in sequencing technologies and multimodal approaches enhance the clinical applicability of ctDNA. Integrating ctDNA with imaging and traditional biomarkers offers a pathway to precision oncology, ultimately improving outcomes. This review underscores the potential of ctDNA to redefine PC management while addressing current limitations and future directions for research and clinical implementation. Full article

Background/Objectives: Hemodialysis catheter-related bloodstream infection (HD-CRBSIs) is a main cause of morbidity in hemodialysis. New preventive strategies have emerged, such as using lock solutions with antiseptic or antibiotic capacity. In this study, the antimicrobial effect was analyzed in vitro and with a catheter model of lock solutions of gentamicin (LSG), gentamicin/heparin (LSG/H), and gentamicin/citrate (LSG/C) in clinical and ATCC strains of Pseudomonas aeruginosa and Staphylococcus aureus. Methods: The formation, minimum inhibitory concentration, and minimum inhibitory concentration of the biofilm and minimum biofilm eradication concentration of the lock solutions were determined. Additionally, colony-forming unit assays were performed to evaluate the antimicrobial efficacy of the lock solutions in a hemodialysis catheter inoculation model. Results: The minimum inhibitory concentration (MIC) of planktonic cells of both P. aeruginosa and S. aureus for LSG/H and LSG/C was 4 µg/mL. In the minimum biofilm inhibitory concentration (MBIC) tests, the LSG/H was less effective than LSG/C, requiring higher concentrations for inhibition, contrary to the minimum biofilm eradication concentration (MBEC), where LSG/H was more effective. All lock solutions eradicated P. aeruginosa biofilms in the HD catheter model under standard conditions. Nevertheless, under modified conditions, the lock solutions were not as effective versus ATCC and clinical strains of S. aureus. Conclusions: Our analysis shows that the lock solutions studied managed to eradicate intraluminal mature P. aeruginosa in non-tunneled HD catheters under standard conditions. Biofilm inhibition and eradication were observed at low gentamicin concentrations, which could optimize the gentamicin concentration in lock solutions used in HD catheters. Full article

In the original randomised Dietary Intervention to Stop Coronary Atherosclerosis (DISCO-CT) trial, a 12-month Dietary Approaches to Stop Hypertension (DASH) project led by dietitians improved cardiovascular and metabolic risk factors and reduced platelet chemokine levels in patients with coronary artery disease (CAD). It is unclear whether these benefits are sustained. Objective: To determine whether the metabolic, inflammatory, and clinical benefits achieved during the DISCO-CT trial are sustained six years after the structured intervention ended. Methods: Ninety-seven adults with non-obstructive CAD confirmed in coronary computed tomography angiography were randomly assigned to receive optimal medical therapy (control group, n = 41) or the same therapy combined with intensive DASH counselling (DASH group, n = 43). After 301 ± 22 weeks, 84 individuals (87%) who had given consent underwent reassessment of body composition, meal frequency assessment, and biochemical testing (lipids, hs-CRP, CXCL4, RANTES and homocysteine). Major adverse cardiovascular events (MACE) were assessed. Results: During the intervention, the DASH group lost an average of 3.6 ± 4.2 kg and reduced their total body fat by an average of 4.2 ± 4.8 kg, compared to an average loss of 1.1 ± 2.9 kg and a reduction in total body fat of 0.3 ± 4.1 kg in the control group (both p < 0.01). Six years later, most of the lost body weight and fat tissue had been regained, and there was a sharp increase in visceral fat area in both groups (p < 0.0001). CXCL4 decreased by 4.3 ± 3.0 ng/mL during the intervention and remained lower than baseline values; in contrast, in the control group, it initially increased and then decreased (p < 0.001 between groups). LDL cholesterol and hs-CRP levels returned to baseline in both groups but remained below baseline in the DASH group. There was one case of MACE in the DASH group, compared with four cases (including one fatal myocardial infarction) in the control group (p = 0.575). Overall adherence to the DASH project increased by 26 points during counselling and then decreased by only four points, remaining higher than in the control group. Conclusions: A one-year DASH project supported by a physician and dietitian resulted in long-term suppression of the proatherogenic chemokine CXCL4 and fewer MACE over six years, despite a decline in adherence and loss of most anthropometric and lipid benefits. It appears that sustained systemic reinforcement of behaviours is necessary to maintain the benefits of lifestyle intervention in CAD. Full article

Background/Objectives: Pressure injuries are a significant concern among older adults, particularly in community-based long-term care settings where prolonged immobility is prevalent. This study aimed to identify factors influencing sacral interface pressure in community-dwelling older adults, with an emphasis on support surface usage and clinical risk indicators. Methods: A total of 210 participants aged 65 years and older, all receiving long-term care services in South Korea, were enrolled in this study. Sacral interface pressure was measured in the supine position using a portable pressure mapping device (Palm Q7). General characteristics, Braden Scale scores, Huhn Scale scores, and mattress usage were assessed. Data were analyzed using descriptive statistics, t-tests, chi-square tests, and logistic regression. Results: Mattress non-use was identified as the strongest predictor of elevated sacral interface pressure (OR = 6.71, p < 0.001), followed by Braden Scale scores indicating moderate risk (OR = 4.8, p = 0.006). Huhn Scale scores were not significantly associated with interface pressure. These results suggest that support surface quality and skin condition have a stronger impact on interface pressure than mobility-related risk factors. Conclusions: The findings highlight the importance of providing high-quality pressure-relieving mattresses and implementing standardized nursing assessments to reduce the risk of pressure injuries. Integrating smart technologies and expanding access to advanced support surfaces may aid in developing tailored preventive strategies for vulnerable older adults. Full article

Background/Objective: Nursing and non-nursing students experience high stress levels, making them susceptible to mental health issues. This study compared stress, anxiety, and depression between these two groups after 2 years of the COVID-19 pandemic. Additionally, it explored the relationship between perceived helplessness, self-efficacy, and symptoms of mental stress and strain resulting from challenging internship conditions for nursing students. Methods: This cross-sectional study included 154 nursing students (mean age = 22.43 years) and 291 non-nursing students (mean age = 27.7 years). Data were collected using the Depression Anxiety Stress Scales (DASS-21), Perceived Stress Scale-10 (PSS-10), and a questionnaire on mental stress and strain. Results: Nursing students reported significantly higher scores in the DASS-21 subscales depression (ηp² = 0.016) and anxiety (ηp² = 0.037), and global stress (PSS-10; ηp² = 0.029) compared to non-nursing students, but no significant difference on the DASS-21 Stress subscale. The observed group differences in the present study may be partially attributed to group differences in demographic factors. Helplessness correlated strongly with nearly all scales of mental stress and strain during internships (all p’s < 0.001), while self-efficacy showed a strong negative correlation with non-occupational difficulties, health impairment, and emotional problems (all p’s < 0.001). Conclusions: Nursing students experience elevated depression, anxiety, and perceived stress levels compared to non-nursing students. Stronger feelings of helplessness and lower confidence in their ability to overcome challenges were strongly correlated with mental stress and strain during clinical training. Targeted interventions such as cognitive behavioral training and stress management should be integrated into nursing curricula to enhance resilience and coping strategies. Full article

(1) Virtual reality (VR) technologies have shown significant potential for diagnosing and treating vision-related impairments. This rapid review evaluates and characterizes the existing literature on VR technologies for diagnosing and treating vision-based diseases. (2) Methods: A systematic search was conducted across Ovid MEDLINE, Ovid Embase, the Cochrane Database of Systematic Reviews (Ovid), and the Cochrane Central Register of Controlled Trials (Ovid). Abstracts were screened using Rayyan QCRI, followed by full-text screening and data extraction. Eligible studies were published in peer-reviewed journals, written in English, focused on human participants, used immersive and portable VR devices as the primary intervention, and reported on the clinical effectiveness of VR for therapeutic, diagnostic, or screening purposes for vision or auditory–visual impairments. Various study characteristics, including design and participant details, were extracted, and the MMAT assessment tool was used to evaluate study quality. (3) Results: Seventy-six studies met the inclusion criteria. Among these, sixty-four (84.2%) were non-randomized studies exploring VR’s effectiveness, while twenty-two (15.8%) were randomized-controlled trials. Of the included studies, 38.2% focused on diagnosing, 21.0% on screening, and 38.2% on treating vision impairments. Glaucoma and amblyopia were the most commonly studied visual impairments. (4) Conclusions: The use of standalone, remotely controlled VR headsets for screening and diagnosing visual diseases represents a promising advancement in ophthalmology. With ongoing technological developments, VR has the potential to revolutionize eye care by improving accessibility, efficiency, and personalization. Continued research and innovation in VR applications for vision care are expected to further enhance patient outcomes. Full article

Multiple sclerosis (MS), a chronic disease of the central nervous system, is known to cause structural and vascular changes in the retina. Although optical coherence tomography (OCT) and fundus photography can detect retinal thinning and circulatory abnormalities, these findings are not specific to MS. This study explores the potential of Infrared Scanning-Laser-Ophthalmoscopy (IR-SLO) imaging to uncover vascular morphological features that may serve as MS-specific biomarkers. Using an age-matched, subject-wise stratified k-fold cross-validation approach, a deep learning model originally designed for color fundus images was adapted to segment optic disc, optic cup, and retinal vessels in IR-SLO images, achieving Dice coefficients of 91%, 94.5%, and 97%, respectively. This process included tailored pre- and post-processing steps to optimize segmentation accuracy. Subsequently, clinically relevant features were extracted. Statistical analyses followed by SHapley Additive exPlanations (SHAP) identified vessel fractal dimension, vessel density in zones B and C (circular regions extending 0.5–1 and 0.5–2 optic disc diameters from the optic disc margin, respectively), along with vessel intensity and width, as key differentiators between MS patients and healthy controls. These findings suggest that IR-SLO can non-invasively detect retinal vascular biomarkers that may serve as additional or alternative diagnostic markers for MS diagnosis, complementing current invasive procedures. Full article

Liquid biopsy has emerged as a valuable tool for the detection and monitoring of colorectal cancer (CRC), providing minimally invasive insights into tumor biology through circulating biomarkers such as circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). Additional biomarkers, including tumor-educated platelets (TEPs) and exosomal RNAs, offer further potential for early detection and prognostic role, although ongoing clinical validation is still needed. This review summarizes the current evidence on the diagnostic, prognostic, and predictive capabilities of liquid biopsy in both metastatic and non-metastatic CRC. In the non-metastatic setting, liquid biopsy is gaining traction in early detection through screening and in identifying minimal residual disease (MRD), potentially guiding adjuvant treatment and reducing overtreatment. In contrast, liquid biopsy is more established in metastatic CRC for monitoring treatment responses, clonal evolution, and mechanisms of resistance. The integration of ctDNA-guided treatment algorithms into clinical practice could optimize therapeutic strategies and minimize unnecessary interventions. Despite promising advances, challenges remain in assay standardization, early-stage sensitivity, and the integration of multi-omic data for comprehensive tumor profiling. Future efforts should focus on enhancing the sensitivity of liquid biopsy platforms, validating emerging biomarkers, and expanding multi-omic approaches to support more targeted and personalized treatment strategies across CRC stages. Full article

Invasive candidiasis (IC), characterized by the most common clinical manifestation of candidemia, is a fungal infection with a high mortality rate and a significant impact on global public health. It is estimated that each year there are between 227,000 and 250,000 hospitalizations related to IC, with more than 100,000 associated deaths. In Latin America and the Caribbean (LA&C), the absence of a standardized surveillance system has led to multicenter studies documenting incidences ranging from 0.74 to 6.0 cases per 1000 hospital admissions, equivalent to 50,000–60,000 hospitalizations annually, with mortality rates of up to 60% in certain high-risk groups. Armed conflicts and structural violence in LA&C cause forced displacement, the collapse of health systems, and poor living conditions—such as overcrowding, malnutrition, and lack of sanitation—which increase vulnerability to opportunistic infections, such as IC. Insufficient specialized laboratories, diagnostic technology, and trained personnel impede pathogen identification and delay timely initiation of antifungal therapy. Furthermore, the empirical use of broad-spectrum antibiotics and the limited availability of echinocandins and lipid formulations of amphotericin B have promoted the emergence of resistant non-albicans strains, such as Candida tropicalis, Candida parapsilosis, and, in recent outbreaks, Candidozyma auris. Full article

Background: Trichosporon spp. are opportunistic fungi, capable of causing infection, especially in critically ill individuals who often use broad-spectrum antibiotics, invasive devices, and have comorbidities. Objectives The aim of this study was to analyze individuals’ clinical characteristics, evaluate tolerance to biocides, as well as biofilm formation and efflux pump activity in isolates of Trichosporon asahii. Methods: Clinical isolates of T. asahii collected between 2020 and 2023 from both hospitalized and non-hospitalized individuals, of both sexes, regardless of age, were tested for tolerance to sodium hypochlorite, hydrogen peroxide, benzalkonium chloride, and ethyl alcohol. Efflux pump activity was also assessed using ethidium bromide, and biofilm formation was measured with the Safranin test. Clinical parameters such as outcomes, source, and length of hospitalization were analyzed through electronic medical records. Results: A total of 37 clinical isolates of T. asahii were identified. Thirty-three (83.8%) isolates were from hospitalized individuals, with 81.82% collected in ICUs, an average hospital stay of 35 days, and a mortality rate of 51.6%. The tested strains displayed the largest mean inhibition zone for 2% sodium hypochlorite, indicating lower tolerance. A high level of efflux pump expression was detected among clinical isolates. Biofilm formation was detected in 25/67.5% of the isolates. Conclusions: These findings highlight the clinical relevance of T. asahii, particularly in critically ill individuals, and underscore the pathogen’s ability to tolerate biocides, express efflux pumps, and form biofilms, all of which may contribute to its persistence and pathogenicity in hospital environments. Enhanced surveillance and effective microbial control measures are essential to mitigate the risks associated with T. asahii infections. Full article