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Search Results (11,588)

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25 pages, 3861 KiB  
Article
Comprehensive Management of Different Types of Pelvic Fractures Through Multiple Disciplines: A Case Series
by Bharti Sharma, Samantha R. Kiernan, Christian Ugaz Valencia, Omolola Akinsola, Irina Ahn, Agron Zuta, George Agriantonis, Navin D. Bhatia, Kate Twelker, Munirah Hasan, Carrie Garcia, Praise Nesamony, Jasmine Dave, Juan Mestre, Zahra Shafaee, Suganda Phalakornkul, Shalini Arora, Saad Bhatti and Jennifer Whittington
J. Clin. Med. 2025, 14(15), 5593; https://doi.org/10.3390/jcm14155593 (registering DOI) - 7 Aug 2025
Abstract
Background: Pelvic fractures are complex injuries often associated with significant morbidity and mortality, requiring multidisciplinary management. This case series highlights the presentation, management strategies, and outcomes of patients with pelvic fractures treated at our institution. Methods: The medical records of 13 patients diagnosed [...] Read more.
Background: Pelvic fractures are complex injuries often associated with significant morbidity and mortality, requiring multidisciplinary management. This case series highlights the presentation, management strategies, and outcomes of patients with pelvic fractures treated at our institution. Methods: The medical records of 13 patients diagnosed with pelvic fractures from 1 January 2020 through 31 December 2023 were retrospectively reviewed. Demographic data, mechanism of injury, fracture pattern, associated injuries, treatment modalities, and outcomes were analyzed. Results: A total of 13 patients were included in the study, with ages ranging from 18–95 years. Six of the patients were male and seven were female. The most common mechanisms of injury were falls and pedestrians struck by vehicles. Associated injuries included traumatic brain injury (TBI), fractures including extremities, ribs, and vertebrae, visceral injury, and spinal cord injury. Treatment strategies ranged from conservative, non-surgical management to operative intervention, including interventional radiology embolization, external traction, open reduction and internal fixation (ORIF), and percutaneous screw stabilization. Additional interventions included chest tube placement, exploratory laparotomy, and craniectomy. Two patients died while in the hospital, one was discharged to a shelter, and the remaining 10 were discharged to various inpatient rehab facilities. Conclusions: Pelvic fractures pose significant clinical challenges due to their complexity and associated injuries. This case series underscores the importance of multidisciplinary intervention and treatment strategies in optimizing outcomes. Further studies should focus on the effectiveness of interventions, utilization of new technology, and multidisciplinary team planning. Full article
15 pages, 1362 KiB  
Article
Surgical and Clinical Aspects Associated with Double-Valve Infective Endocarditis
by Sonia Lerta, Gloria Sangaletti, Vincenzo Antonio Villano, Flavia Puci, Eraldo Kushta, Pasquale Totaro, Filippo Amoroso, Giulia Magrini, Pietro Valsecchi, Raffaele Bruno and Elena Seminari
J. Clin. Med. 2025, 14(15), 5589; https://doi.org/10.3390/jcm14155589 - 7 Aug 2025
Abstract
Background: Double-valve infective endocarditis (DVIE) accounts for 15–20% of all endocarditis and represents a challenge due to the increased incidence of embolic events and congestive heart failure compared to infective endocarditis (IE) affecting one valve. This study aims to evaluate patients’ characteristics, [...] Read more.
Background: Double-valve infective endocarditis (DVIE) accounts for 15–20% of all endocarditis and represents a challenge due to the increased incidence of embolic events and congestive heart failure compared to infective endocarditis (IE) affecting one valve. This study aims to evaluate patients’ characteristics, surgical procedures, complications, and mortality associated with DVIE in our tertiary hospital in Italy. The Endocarditis Registry STEADY includes patients admitted with IE from January 2009 to March 2024 (n = 398). Sixty-three of them (16%) had DVIE. Methods: We conducted a retrospective single-center observational study, analyzing demographic, clinical, and microbiological data in DVIE patients, comparing those treated surgically (surgical group, SG) with those treated medically (non-surgical group, NSG). Results: The groups were homogeneous in age, microbiological yields, type of valve involved, and risk factors for infective endocarditis. The surgical group presented significantly more cancer history, intracardiac complications, and new-onset arrhythmias compared to the non-surgical group. Median hospital stay was similar in both groups. In SG, the most common postoperative complication was new rhythm disorders; other complications such as cardiac tamponade, pericardial effusion, and pneumothorax were rare. In-hospital mortality was similar between groups; however, one-year survival was higher in the surgical group (72% vs. 54%, p = 0.031). In our series, 16 patients were over 75 years old (25%), and 7 of them (44%) underwent cardiac surgery. One-year survival in the surgical group was also higher in this subgroup. Conclusions: Surgical treatment, when indicated, may improve the prognosis of patients with DVIE, including elderly patients. Full article
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18 pages, 549 KiB  
Article
Clinical Evaluation of Ripasudil for Corneal Edema: A Large-Scale Retrospective Cohort Study
by Nir Erdinest, Michael Tabi, Nadav Shemesh, Jamel Corredores, Claudia Yahalom, Yossi Eshel, Benjamin Stern, David Smadja, Zvi Gur and Itay Lavy
J. Clin. Med. 2025, 14(15), 5572; https://doi.org/10.3390/jcm14155572 - 7 Aug 2025
Abstract
Objectives: This study evaluated the therapeutic potential of topical Ripasudil hydrochloride hydrate in managing various forms of corneal edema. Methods: This retrospective study included 96 patients of 72.20 ± 10.52 years, with 53 females (55.2%) who were treated with Ripasudil for corneal edema, [...] Read more.
Objectives: This study evaluated the therapeutic potential of topical Ripasudil hydrochloride hydrate in managing various forms of corneal edema. Methods: This retrospective study included 96 patients of 72.20 ± 10.52 years, with 53 females (55.2%) who were treated with Ripasudil for corneal edema, with a mean treatment duration of 5.2 ± 2.3 months, divided into four groups: post-cataract surgery (n = 32), Fuchs endothelial corneal dystrophy (FECD; n = 29), post-Descemet membrane endothelial keratoplasty (DMEK; n = 25), and post-penetrating keratoplasty (PKP; n = 10). All patients were treated with Ripasudil, typically administered three times daily in the first week and twice daily in the following months. Clinical efficacy outcomes were assessed using changes in best-corrected visual acuity (BCVA), central corneal thickness (CCT), and endothelial cell count (ECC) with specular microscopy, anterior segment optical coherence tomography (OCT), and slit-lamp examination, while intraocular pressure (IOP) was measured using the iCare tonometer. Results: Ripasudil treatment led to a reduction in CCT and improvement in visual acuity across most groups, with minimal changes in ECC. CCT decreased by 30.44 μm (p < 0.001), 25.56 μm (p < 0.001), 8.41 μm (p = 0.05), and 6.80 μm (p > 0.1); visual acuity improved by 0.27 (p = 0.001), 0.18 (p = 0.02), 0.17 (p = 0.025), and 0.07 logMAR units (p > 0.1); and ECC changed by +7.0 (p > 0.1), 15.4 (p > 0.1), −7.6 (p > 0.1), and 2.3 cells/mm2 (p > 0.1) in the post-cataract surgery, FECD, post-DMEK, and post-PKP groups, respectively. Conclusions: No adverse events or progression of edema were recorded during the follow-up period. These findings support the role of Ripasudil as a non-invasive pharmacological approach to managing corneal edema and delaying or possibly avoiding surgical interventions, such as corneal transplantation, in selected cases. Full article
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28 pages, 3469 KiB  
Review
Prostate Cancer Treatments and Their Effects on Male Fertility: Mechanisms and Mitigation Strategies
by Aris Kaltsas, Nikolaos Razos, Zisis Kratiras, Dimitrios Deligiannis, Marios Stavropoulos, Konstantinos Adamos, Athanasios Zachariou, Fotios Dimitriadis, Nikolaos Sofikitis and Michael Chrisofos
J. Pers. Med. 2025, 15(8), 360; https://doi.org/10.3390/jpm15080360 - 7 Aug 2025
Abstract
Prostate cancer (PCa) is the second most frequently diagnosed malignancy in men worldwide. Although traditionally considered a disease of older men, the incidence of early-onset PCa (diagnosis < 55 years) is steadily rising. Advances in screening and therapy have significantly improved survival, creating [...] Read more.
Prostate cancer (PCa) is the second most frequently diagnosed malignancy in men worldwide. Although traditionally considered a disease of older men, the incidence of early-onset PCa (diagnosis < 55 years) is steadily rising. Advances in screening and therapy have significantly improved survival, creating a growing cohort of younger survivors for whom post-treatment quality of life—notably reproductive function—is paramount. Curative treatments such as radical prostatectomy, pelvic radiotherapy, androgen-deprivation therapy (ADT), and chemotherapy often cause irreversible infertility via multiple mechanisms, including surgical disruption of the ejaculatory tract, endocrine suppression of spermatogenesis, direct gonadotoxic injury to the testes, and oxidative sperm DNA damage. Despite these risks, fertility preservation is frequently overlooked in pre-treatment counseling, leaving many patients unaware of their options. This narrative review synthesizes current evidence on how PCa therapies impact male fertility, elucidates the molecular and physiological mechanisms of iatrogenic infertility, and evaluates both established and emerging strategies for fertility preservation and restoration. Key interventions covered include sperm cryopreservation, microsurgical testicular sperm extraction (TESE), and assisted reproductive technologies (ART). Psychosocial factors influencing decision-making, novel biomarkers predictive of post-treatment spermatogenic recovery, and long-term offspring outcomes are also examined. The review underscores the urgent need for timely, multidisciplinary fertility consultation as a routine component of PCa care. As PCa increasingly affects men in their reproductive years, proactively integrating preservation into standard oncologic practice should become a standard survivorship priority. Full article
(This article belongs to the Special Issue Clinical Advances in Male Genitourinary and Sexual Health)
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15 pages, 1713 KiB  
Review
Current Developments of Iron Oxide Nanomaterials as MRI Theranostic Agents for Pancreatic Cancer
by Fong-Yu Cheng, Boguslaw Tomanek and Barbara Blasiak
J. Nanotheranostics 2025, 6(3), 22; https://doi.org/10.3390/jnt6030022 - 7 Aug 2025
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive type of pancreatic cancer. PDAC is difficult to diagnose due to a lack of symptoms in early stages, resulting in a survival rate of less than 10%. Moreover, often cancerous tissues cannot be surgically resected [...] Read more.
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive type of pancreatic cancer. PDAC is difficult to diagnose due to a lack of symptoms in early stages, resulting in a survival rate of less than 10%. Moreover, often cancerous tissues cannot be surgically resected due to their deep abdomen location. Therefore, early detection is the essential strategy enabling effective PDAC treatment. Over the past few years, the development of nanomaterials for Magnetic Resonance Imaging (MRI) has expanded and improved imaging quality and diagnostic accuracy. Nanomaterials can be currently designed, manufactured and synthesized with other structures to provide improved diagnosis and advanced therapy. Although MRI equipped with the innovative nanomaterials became a powerful tool for the diagnosis and treatment of patients with various cancers, the detection of PDAC remains challenging. Nevertheless, recent advancements in PDAC theranostics provided progress in the detection and treatment of this challenging type of cancer. Present research in this area is focused on suitable carriers, eliminating delivery barriers, and the development of efficient anti-cancer drugs. Herein we discuss the current applications of iron oxide nanoparticles to the MRI diagnosis and treatment of pancreatic cancer. Full article
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13 pages, 1146 KiB  
Article
Non-Descemet Stripping Automated Endothelial Keratoplasty (nDSAEK) for Late Endothelial Failure After Mushroom Keratoplasty: A Retrospective Analysis of Visual and Anatomical Outcomes
by Antonio Moramarco, Natalie di Geronimo, Marian Sergiu Zimbru, Arianna Grendele, Francesco Biagini, Maurizio Mete, Vito Romano and Luigi Fontana
J. Clin. Med. 2025, 14(15), 5568; https://doi.org/10.3390/jcm14155568 - 7 Aug 2025
Abstract
Background: Mushroom penetrating keratoplasty (MPK) is an alternative to traditional penetrating keratoplasty (PK) that offers improved graft survival and reduced immunological rejection. However, MPK grafts may still experience endothelial failure over time. This study evaluates the outcomes of non-Descemet Stripping Automated Endothelial [...] Read more.
Background: Mushroom penetrating keratoplasty (MPK) is an alternative to traditional penetrating keratoplasty (PK) that offers improved graft survival and reduced immunological rejection. However, MPK grafts may still experience endothelial failure over time. This study evaluates the outcomes of non-Descemet Stripping Automated Endothelial Keratoplasty (nDSAEK) as a surgical approach for endothelial decompensation following MPK. Methods: A monocentric, retrospective study was conducted at the Ophthalmology Department of Sant’Orsola-Malpighi Hospital, including patients who underwent nDSAEK for endothelial failure after MPK between 2022 and 2024. Pre- and postoperative best-corrected visual acuity (BCVA), central corneal thickness (CCT), and endothelial cell density (ECD) were assessed. Results: Eighteen eyes from 18 patients (mean age: 39.94 years) were included. Primary MPK indications were post-keratitis leucoma (77.7%), traumatic scarring (16.7%), and keratoconus (5.6%). At one year, mean BCVA improved significantly from 1.40 ± 0.42 logMAR to 0.46 ± 0.19 logMAR (p < 0.05), and mean CCT decreased from 721 ± 70.12 µm to 616 ± 52.80 µm (p < 0.05). The mean postoperative ECD was 1748 ± 100 cells/mm2, with lower eye values requiring re-bubbling. No immunological rejection or graft failures were reported. Conclusions: nDSAEK is a promising treatment for MPK endothelial failure, demonstrating good visual and anatomical outcomes. Full article
(This article belongs to the Section Ophthalmology)
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12 pages, 1519 KiB  
Article
Arthroscopic Repair Versus Conservative Treatment in Degenerative Cuff Tears: Midterm Results
by Maria Rosario Camacho-Sanchez, Irene Calzado-Alvarez, Jose Carlos Minarro, Diana Maria Dussan-Arango, Clementina López-Medina and Alberto Izquierdo-Fernandez
Life 2025, 15(8), 1254; https://doi.org/10.3390/life15081254 - 7 Aug 2025
Abstract
(1) Background and aim: The benefit of surgical treatment compared to conservative management is unclear in degenerative cuff tears, and there is limited evidence regarding midterm functional outcomes. This study sought to compare the midterm functional outcomes of surgical versus conservative treatment for [...] Read more.
(1) Background and aim: The benefit of surgical treatment compared to conservative management is unclear in degenerative cuff tears, and there is limited evidence regarding midterm functional outcomes. This study sought to compare the midterm functional outcomes of surgical versus conservative treatment for rotator cuff tears. (2) Methods: All patients on the waiting list for arthroscopy of cuff tears in a single center between 2013 and 2015 were analyzed. They were divided into two groups: those who underwent surgery (arthroscopy group) and those who declined the procedure (orthopedic group). The primary endpoint was shoulder functionality, evaluated with the CMS, SST, and SPADI-SP questionnaires. Inverse probability of treatment weighting (IPTW) was used to account for differences between the groups. (3) Results: Of 57 patients (67 (62–71) years old, 47% women), 32 were in the arthroscopy group and 25 in the orthopedic group. Functionality was assessed at a median of 7 (7–8) years after diagnosis. The patients in the arthroscopy group were younger (p = 0.023) and more frequently women (p = 0.074). No significant differences were observed in the type of tear (p = 0.205) or laterality (p = 0.164). Functional outcome analysis showed more favorable scores in the surgical group: constant (74.5 ± 16.6 vs. 58.4 ± 23, p = 0.016), SST (7.3 ± 3.1 vs. 4.9 ± 4.2, p = 0.016), and SPADI-SP (35.7 ± 26.6 vs. 56.1 ± 30.4, p = 0.006). (4) Conclusions: In this cohort of patients with cuff tears, arthroscopic repair was associated with better clinical and functional midterm results compared to conservative treatment, although the benefit was less evident in older patients and those with complete tears. Full article
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25 pages, 1054 KiB  
Review
Gut Feeling: Biomarkers and Biosensors’ Potential in Revolutionizing Inflammatory Bowel Disease (IBD) Diagnosis and Prognosis—A Comprehensive Review
by Beatriz Teixeira, Helena M. R. Gonçalves and Paula Martins-Lopes
Biosensors 2025, 15(8), 513; https://doi.org/10.3390/bios15080513 - 7 Aug 2025
Abstract
Inflammatory Bowel Diseases (IBDs) are complex, multifactorial disorders with no known cure, necessitating lifelong care and often leading to surgical interventions. This ongoing healthcare requirement, coupled with the increased use of biological drugs and rising disease prevalence, significantly increases the financial burden on [...] Read more.
Inflammatory Bowel Diseases (IBDs) are complex, multifactorial disorders with no known cure, necessitating lifelong care and often leading to surgical interventions. This ongoing healthcare requirement, coupled with the increased use of biological drugs and rising disease prevalence, significantly increases the financial burden on the healthcare systems. Thus, a number of novel technological approaches have emerged in order to face some of the pivotal questions still associated with IBD. In navigating the intricate landscape of IBD, biosensors act as indispensable allies, bridging the gap between traditional diagnostic methods and the evolving demands of precision medicine. Continuous progress in biosensor technology holds the key to transformative breakthroughs in IBD management, offering more effective and patient-centric healthcare solutions considering the One Health Approach. Here, we will delve into the landscape of biomarkers utilized in the diagnosis, monitoring, and management of IBD. From well-established serological and fecal markers to emerging genetic and epigenetic markers, we will explore the role of these biomarkers in aiding clinical decision-making and predicting treatment response. Additionally, we will discuss the potential of novel biomarkers currently under investigation to further refine disease stratification and personalized therapeutic approaches in IBD. By elucidating the utility of biosensors across the spectrum of IBD care, we aim to highlight their importance as valuable tools in optimizing patient outcomes and reducing healthcare costs. Full article
(This article belongs to the Special Issue Feature Papers of Biosensors)
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15 pages, 3724 KiB  
Article
Exploring the Association Between Multidimensional Dietary Patterns and Non-Scarring Hair Loss Using Mendelian Randomization
by Lingfeng Pan, Philipp Moog, Caihong Li, Leonard Steinbacher, Samuel Knoedler, Haydar Kükrek, Ulf Dornseifer, Hans-Günther Machens and Jun Jiang
Nutrients 2025, 17(15), 2569; https://doi.org/10.3390/nu17152569 - 7 Aug 2025
Abstract
Background: Androgenetic alopecia (AGA) and alopecia areata (AA) impose significant psychosocial burdens. While pharmacological and surgical treatments exist, the role of dietary factors remains underexplored due to methodological limitations in observational studies. This Mendelian randomization (MR) study investigates causal relationships between 187 dietary [...] Read more.
Background: Androgenetic alopecia (AGA) and alopecia areata (AA) impose significant psychosocial burdens. While pharmacological and surgical treatments exist, the role of dietary factors remains underexplored due to methodological limitations in observational studies. This Mendelian randomization (MR) study investigates causal relationships between 187 dietary exposures and hair loss, leveraging genetic variants to address confounding biases. Methods: Genome-wide association study (GWAS) data from 161,625 UK Biobank participants were analyzed, focusing on food preferences and intake patterns. Genetic instruments for each of the 187 dietary exposures were selected at a genome-wide significance threshold (p < 5 × 10−8), with rigorous sensitivity analyses (MR-Egger, MR-PRESSO) to validate causality. Outcomes included AA and AGA datasets from the FinnGen consortium. Results: MR analysis identified 18 specific dietary exposures significantly associated with non-scarring hair loss (FDR < 0.05). Protective effects emerged for antioxidant-rich dietary exposures, represented by higher preferences for melon, onions, and tea. Elevated risks were observed for certain exposures, including croissants, goat cheese, and whole milk. Alcohol consumption exhibited the strongest risk associations. Our extensive analysis of alcohol intake, combining data from multiple studies, consistently identified it as a significant risk factor for both alopecia areata and androgenetic alopecia. Conclusions: These findings imply modifiable dietary patterns in hair loss pathophysiology. A dual strategy is proposed: prioritizing polyphenol-rich plant foods while minimizing pro-inflammatory triggers like processed carbohydrates and alcohol. Clinically, tailored dietary adjustments—reducing ultra-processed foods and alcohol—may complement existing therapies for hair loss management. Full article
(This article belongs to the Section Nutrition and Metabolism)
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21 pages, 880 KiB  
Review
Regenerative Cartilage Treatment for Focal Chondral Defects in the Knee: Focus on Marrow-Stimulating and Cell-Based Scaffold Approaches
by Filippo Migliorini, Francesco Simeone, Tommaso Bardazzi, Michael Kurt Memminger, Gennaro Pipino, Raju Vaishya and Nicola Maffulli
Cells 2025, 14(15), 1217; https://doi.org/10.3390/cells14151217 - 7 Aug 2025
Abstract
Focal chondral defects of the knee are a common cause of pain and functional limitation in active individuals and may predispose to early degenerative joint changes. Given the limited regenerative capacity of hyaline cartilage, biologically based surgical strategies have emerged to promote tissue [...] Read more.
Focal chondral defects of the knee are a common cause of pain and functional limitation in active individuals and may predispose to early degenerative joint changes. Given the limited regenerative capacity of hyaline cartilage, biologically based surgical strategies have emerged to promote tissue repair and restore joint function. This narrative review critically examines current treatment approaches that rely on autologous cell sources and scaffold-supported regeneration. Particular emphasis is placed on techniques that stimulate endogenous repair or support chondrocyte-based tissue restoration through the use of autologous biomaterial constructs. The influence of lesion morphology, joint biomechanics, and patient-specific variables on treatment selection is discussed in detail, focusing on the differences between tibiofemoral and patellofemoral involvement. Biologically driven approaches have shown promising mid- to long-term outcomes in selected patients, and are increasingly favoured over traditional methods in specific clinical scenarios. However, the literature remains limited by heterogeneity in study design, follow-up duration, and outcome measures. This review aims to provide an evidence-based, morphology-informed framework to support the clinical decision-making process in the management of knee cartilage defects. Full article
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15 pages, 1304 KiB  
Review
Calcific Aortic Valve Stenosis: A Focal Disease in Older and Complex Patients—What Could Be the Best Time for an Appropriate Interventional Treatment?
by Annamaria Mazzone, Augusto Esposito, Ilenia Foffa and Sergio Berti
J. Clin. Med. 2025, 14(15), 5560; https://doi.org/10.3390/jcm14155560 - 7 Aug 2025
Abstract
Calcific aortic stenosis (CAS) is a newly emerging pandemic in elderly individuals due to the aging of the population in the world. Surgical Aortic Valve Replacement (SAVR) and Transcatheter Aortic Valve Replacement (TAVR) are the cornerstone of the management of severe aortic stenosis [...] Read more.
Calcific aortic stenosis (CAS) is a newly emerging pandemic in elderly individuals due to the aging of the population in the world. Surgical Aortic Valve Replacement (SAVR) and Transcatheter Aortic Valve Replacement (TAVR) are the cornerstone of the management of severe aortic stenosis accompanied by one or more symptoms. Moreover, an appropriate interventional treatment of CAS, in elderly patients, is a very complex decision for heart teams, to avoid bad outcomes such as operative mortality, cardiovascular and all-cause death, hospitalization for heart failure, worsening of quality of life. In fact, CAS in the elderly is not only a focal valve disease, but a very complex clinical picture with different risk factors and etiologies, differing underlying pathophysiology, large phenotypic heterogeneity in a context of subjective biological, phenotypic and functional aging until frailty and disability. In this review, we analyzed separately and in a more integrated manner, the natural and prognostic histories of the progression of aortic stenosis, the phenotypes of myocardial damage and heart failure, within the metrics and aging trajectory. The aim is to suggest, during the clinical timing of valve disease, the best interval time for an appropriate and effective interventional treatment in each older patient, beyond subjective symptoms by integration of clinical, geriatric, chemical, and advanced imaging biomarkers. Full article
(This article belongs to the Section Cardiology)
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18 pages, 3441 KiB  
Review
Epidermal Growth Factor Receptor (EGFR)-Targeting Peptides and Their Applications in Tumor Imaging Probe Construction: Current Advances and Future Perspectives
by Lu Huang, Ying Dong, Jinhang Li, Xinyu Yang, Xiaoqiong Li, Jia Wu, Jinhua Huang, Qiaoxuan Zhang, Zemin Wan, Shuzhi Hu, Ruibing Feng, Guodong Li, Xianzhang Huang and Pengwei Zhang
Biology 2025, 14(8), 1011; https://doi.org/10.3390/biology14081011 - 7 Aug 2025
Abstract
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, [...] Read more.
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
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18 pages, 435 KiB  
Review
Molecular and Glycosylation Pathways in Osteosarcoma: Tumor Microenvironment and Emerging Strategies Toward Personalized Oncology
by Georgian Longin Iacobescu, Antonio-Daniel Corlatescu, Horia Petre Costin, Razvan Spiridonica, Mihnea-Ioan-Gabriel Popa and Catalin Cirstoiu
Curr. Issues Mol. Biol. 2025, 47(8), 629; https://doi.org/10.3390/cimb47080629 - 7 Aug 2025
Abstract
Osteosarcoma (OS) is the most common primary bone malignancy in children and adolescents, which is also considered an aggressive disease due to its rapid growth rate, ability to metastasize early, and complex and heterogeneous tumor microenvironment (TME). Although we are developing improved surgical [...] Read more.
Osteosarcoma (OS) is the most common primary bone malignancy in children and adolescents, which is also considered an aggressive disease due to its rapid growth rate, ability to metastasize early, and complex and heterogeneous tumor microenvironment (TME). Although we are developing improved surgical and chemotherapeutic approaches, the presence of metastatic or recurrent disease is still detrimental to the patient’s outcome. Major advances in understanding the molecular mechanisms of OS are needed to substantially improve outcomes for patients being treated for OS. This review integrates new data on the molecular biology, pathophysiology, and immune landscape of OS, as well as introducing salient areas of tumorigenesis underpinning these findings, such as chromothripsis; kataegis; cancer stem cell dynamics; and updated genetic, epigenetic, and glycosylation modifiers. In addition, we review promising biomarkers, diagnostic platforms, and treatments, including immunotherapy, targeted small molecule inhibitors, and nanomedicine. Using genomic techniques, we have defined OS for its significant genomic instability due to TP53 and RB1 mutations, chromosomal rearrangements, and aberrant glycosylation. The TME is also characterized as immunosuppressive and populated by tumor-associated macrophages, myeloid-derived suppressor cells, and regulatory T cells, ultimately inhibiting immune checkpoint inhibitors. Emerging fields such as glycomics and epigenetics, as well as stem cell biology, have defined promising biomarkers and targets. Preclinical studies have identified that glycan-directed CAR therapies could be possible, as well as metabolic inhibitors and 3D tumor models, which presented some preclinical success and could allow for tumoral specificity and enhanced efficacy. OS is a biologically and clinically complex disease; however, advances in exploring the molecular and immunologic landscape of OS present new opportunities in biomarkers and the development of new treatment options with adjunctive care. Successful treatments in the future will require personalized, multi-targeted approaches to account for tumor heterogeneity and immune evasion. This will help us turn the corner in providing improved outcomes for patients with this resilient malignancy. Full article
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17 pages, 2609 KiB  
Article
Residual Tumor Resection After Anti-PD-1 Therapy: A Promising Treatment Strategy for Overcoming Immune Evasive Phenotype Induced by Anti-PD-1 Therapy in Gastric Cancer
by Hajime Matsuida, Kosaku Mimura, Shotaro Nakajima, Katsuharu Saito, Sohei Hayashishita, Chiaki Takiguchi, Azuma Nirei, Tomohiro Kikuchi, Hiroyuki Hanayama, Hirokazu Okayama, Motonobu Saito, Tomoyuki Momma, Zenichiro Saze and Koji Kono
Cells 2025, 14(15), 1212; https://doi.org/10.3390/cells14151212 - 6 Aug 2025
Abstract
Background: Anti-programmed death 1 receptor (PD-1) therapy is a promising treatment strategy for patients with unresectable advanced or recurrent gastric/gastroesophageal junction (G/GEJ) cancer. However, its response rate and survival benefits are still limited; an immunological analysis of the residual tumor after anti-PD-1 therapy [...] Read more.
Background: Anti-programmed death 1 receptor (PD-1) therapy is a promising treatment strategy for patients with unresectable advanced or recurrent gastric/gastroesophageal junction (G/GEJ) cancer. However, its response rate and survival benefits are still limited; an immunological analysis of the residual tumor after anti-PD-1 therapy would be important. Methods: We evaluated the clinical efficacy of tumor resection (TR) after chemotherapy or anti-PD-1 therapy in patients with unresectable advanced or recurrent G/GEJ cancer and analyzed the immune status of tumor microenvironment (TME) by immunohistochemistry using their surgically resected specimens. Results: Patients treated with TR after anti-PD-1 therapy had significantly longer survival compared to those treated with chemotherapy and anti-PD-1 therapy alone. Expression of human leukocyte antigen (HLA) class I and major histocompatibility complex (MHC) class II on tumor cells was markedly downregulated after anti-PD-1 therapy compared to chemotherapy. Furthermore, the downregulation of HLA class I may be associated with the activation of transforming growth factor-β signaling pathway in the TME. Conclusions: Immune escape from cytotoxic T lymphocytes may be induced in the TME in patients with unresectable advanced or recurrent G/GEJ cancer after anti-PD-1 therapy due to the downregulation of HLA class I and MHC class II expression on tumor cells. TR may be a promising treatment strategy for these patients when TR is feasible after anti-PD-1 therapy. Full article
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14 pages, 340 KiB  
Article
FLOT Versus CROSS—What Is the Optimal Therapeutic Approach for Locally Advanced Adenocarcinoma of the Esophagus and the Esophagogastric Junction?
by Martin Leu, Hannes Mahler, Johanna Reinecke, Ute Margarethe König, Leif Hendrik Dröge, Manuel Guhlich, Benjamin Steuber, Marian Grade, Michael Ghadimi, Volker Ellenrieder, Stefan Rieken and Alexander Otto König
Cancers 2025, 17(15), 2587; https://doi.org/10.3390/cancers17152587 - 6 Aug 2025
Abstract
Background/Objectives: Neoadjuvant radiochemotherapy and perioperative chemotherapy are both well-established treatment strategies for locally advanced adenocarcinoma of the esophagus (EAC) and the esophagogastric junction (AEGJ). However, recent knowledge controversially discusses whether neoadjuvant radiotherapy or perioperative chemotherapy represents superior therapeutic options to prolong survival or [...] Read more.
Background/Objectives: Neoadjuvant radiochemotherapy and perioperative chemotherapy are both well-established treatment strategies for locally advanced adenocarcinoma of the esophagus (EAC) and the esophagogastric junction (AEGJ). However, recent knowledge controversially discusses whether neoadjuvant radiotherapy or perioperative chemotherapy represents superior therapeutic options to prolong survival or cause less toxicity. Methods: We retrospectively analyzed 76 patients with locally advanced EAC or AEGJ treated at our tertiary cancer center between January 2015 and March 2023. Patients received either perioperative FLOT chemotherapy (n = 36) or neoadjuvant radiochemotherapy following the CROSS protocol (n = 40), followed by surgical resection and standardized follow-up. We compared survival outcomes, toxicity profiles, treatment compliance, and surgical results between the two groups. Results: There were no statistically significant differences between FLOT and CROSS treatments in five-year loco-regional controls (LRC: 61.5% vs. 68.6%; p = 0.81), progression-free survival (PFS: 33.9% vs. 42.8%; p = 0.82), overall survival (OS: 60.2% vs. 63.4%; p = 0.91), or distant controls (DC: 42.1% vs. 56.5%; p = 0.39). High-grade hematologic toxicities did not significantly differ between groups (p > 0.05). Treatment compliance was lower in the FLOT group, with 50% (18/36) not completing all the planned chemotherapy cycles, compared to 17.5% (7/40) in the CROSS group. All the patients in the CROSS group received the full radiotherapy dose. Surgical outcomes and post-surgical tumor status were comparable between the groups. Conclusions: Although perioperative chemotherapy with FLOT has recently become a standard of care for locally advanced EAC and AEGJ, neoadjuvant radiochemotherapy per the CROSS protocol remains a well-tolerated alternative. In appropriately selected patients, both approaches yield comparable oncological outcomes. Full article
(This article belongs to the Special Issue Current Treatments of Esophageal and Esophagogastric Junction Cancers)
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