Search Results (15,177)

Oral wound healing is a robust process; however, complications from surgery, systemic diseases, and aging can impair healing. While some treatments exist, regenerative therapies to promote mucosal wound healing remain limited. In recent years, there has been a significant rise in FDA-approved cell-based therapies; however, extracellular vesicles represent an emerging cell-free alternative that may mitigate risks associated with cellular therapies, including tumorigenesis and immunogenicity. These lipid-encapsulated nanovesicles can deliver therapeutic cargo, such as proteins, lipids, nucleic acids, or drugs, to the wound site. Extracellular vesicles can be derived from mesenchymal stromal cells, immune cells, bodily fluids, or bacteria, and engineered through genetic modification, preconditioning, or direct cargo loading to enhance therapeutic potency. Furthermore, advanced delivery platforms, including hydrogels, microneedles, and aerosols, allow for sustained and localized EV delivery to the oral wound site. This review examines differences between cutaneous and oral wound healing; factors that impair oral repair; extracellular vesicle sources and engineering strategies; and delivery strategies for developing EV-based therapeutics for oral wound healing. Full article

Background: Robotic-assisted navigational bronchoscopy (RNB) using the ION system (Intuitive Surgical, Sunnyvale, CA, USA) combined with cone-beam computed tomography (CBCT) (Cios Spin, Siemens Healthineers, Erlangen, Germany) and tool-in-lesion verification enables precise diagnosis of peripheral pulmonary nodules. Integrating RNB with intraoperative frozen section analysis may allow same-day resection, avoiding delays between diagnosis and treatment. Standard airway management with a single-lumen tube (SLT) limits immediate transition to lung resection, whereas initial double-lumen tube (DLT) placement could streamline workflow and improve safety. This study evaluated the diagnostic performance, procedural efficiency, and feasibility of an integrated ION-guided RNB workflow using either SLT or DLT. Methods: In this single-center retrospective study, 36 consecutive patients undergoing ION-guided RNB for pulmonary nodules between August 2024 and June 2025 were analyzed. Airway management (SLT vs. DLT) was selected based on surgical planning. Lesions were targeted using CBCT or C-arm fluoroscopy, and biopsies were performed via forceps or cryoprobes. Frozen section results guided immediate surgical resection when malignancy was confirmed. Results: Thirty-six patients (mean age 64.9 ± 7.9 years; female/male ratio 16/20) with 42 nodules (mean diameter 1.22 ± 0.76 cm) were included; 76.2% were peripheral. Mean RNB time was 58.3 ± 21.3 min. Overall diagnostic yield was 73.0%, significantly higher with DLT versus SLT (84.2% vs. 50.0%, p = 0.035), with more biopsies per patient (7.9 ± 2.2 vs. 3.2 ± 3.1, p = 0.035). No major complications occurred. Conclusions: ION-guided RNB with CBCT and intraoperative frozen section enables accurate, single-session diagnosis and treatment of pulmonary nodules. Upfront DLT placement facilitates procedural efficiency within a streamlined “one-stop-shop” workflow without compromising diagnostic yield. Full article

In recent years, dietary intervention has garnered significant attention for T2DM prevention and adjunctive treatment. Lentinula edodes (commonly known as shiitake mushroom), a common edible fungus, has been demonstrated to improve T2DM, primarily attributed to its main bioactive components like peptides and polysaccharides, while their synergistic characteristics are still not fully explained. Therefore, this study investigated the anti-T2DM molecular mechanisms of L. edodes peptides and polysaccharides by integrating network pharmacology and molecular docking. First, systematic searches of the PubMed and HERB databases using keywords such as “Lentinula edodes peptides”, “Lentinula edodes polysaccharides” and “T2DM” and “Lentinula edodes/shiitake mushroom” yielded 25 peptides and 14 polysaccharides. Second, network pharmacology analysis revealed 541 common interaction targets between these peptides/polysaccharides and T2DM. Topological analysis further identified nine core targets: ESR1, MAPK1, AKT1, SRC, EGFR, STAT3, JUN, PIK3CA, and PIK3R1. Third, pathway enrichment analysis showed that these core targets were significantly enriched within the PI3K-Akt signaling pathway and the AGE-RAGE signaling pathway in diabetic complications, suggesting potential anti-T2DM effects through regulation of these key pathways. Finally, molecular docking validation ensured strong binding affinities between peptides/polysaccharides and some core targets, with particularly prominent binding capacities observed for peptides VF and LDELEK with EGFR; peptides KIGSRSRFDVT, LDYGKL, and EDLRLP along with polysaccharides D-glucan and β-glucan with PIK3CA; and peptide DVFAHF with PIK3R1. In summary, this study revealed that L. edodes peptides and polysaccharides may exert synergistic anti-T2DM effects via the regulation of key signaling pathways, including the PI3K-Akt signaling pathway, EGFR tyrosine kinase inhibitor resistance, and the AGE-RAGE signaling pathway in diabetic complications, through their actions on critical targets such as ESR1, PIK3CA, and PIK3R1. These results offer a synergistic mechanism for the anti-T2DM effect of L. edodes, which could be helpful for the development of functional foods and drugs derived from L. edodes. Full article

Obstructive sleep apnea (OSA) is a common disorder caused by recurrent upper airway obstruction during sleep, affecting individuals across the lifespan. In children, OSA commonly results from adenotonsillar hypertrophy and may resolve spontaneously or following surgical intervention. Among adolescents and adults, OSA is more frequently associated with modifiable lifestyle factors, particularly obesity. The natural history of OSA may evolve from intermittent snoring and mild disease to moderate or severe forms if left untreated, leading to reduced health-related quality of life and overall health deterioration. Early identification of OSA, especially in mild and moderate cases, allows timely interventions to improve OSA-associated indices and may prevent progression to severe disease. Continuous positive airway pressure therapy remains the treatment of choice for adults, providing effective symptom control and reducing long-term complications, although adherence rates vary. In obese patients, sustained weight reduction represents the most effective disease-modifying strategy: a ≥5% weight loss is associated with an approximately 80% reduction in progression risk, while bariatric surgery achieves remission in up to 60–65% of cases at one year. Emerging anti-obesity pharmacotherapies have also demonstrated clinically meaningful reductions in the apnea–hypopnea index. Comorbid conditions such as hypertension, type 2 diabetes, and depression exacerbate OSA severity, impair treatment response, and complicate overall disease management. This review uniquely integrates pediatric and adult longitudinal data, treatment-modified trajectories, and emerging therapeutic approaches to provide a life-course perspective on OSA natural history, highlighting opportunities for early, phenotype-directed intervention to possibly alter disease course and long-term outcomes. Full article

Ocular disorders such as keratitis, glaucoma, age-related macular degeneration (AMD), diabetic retinopathy (DR), and dry eye disease (DED) are highly prevalent worldwide and remain major causes of visual impairment and blindness. Conventional therapeutic approaches for ocular diseases, such as eye drops, surgery, and laser therapy, are frequently hampered by limited drug bioavailability, rapid clearance, and treatment-related complications, primarily due to the eye’s unique anatomical and physiological barriers. Hydrogels, characterized by their three-dimensional network structure, high water content, excellent biocompatibility, and tunable physicochemical properties, have emerged as promising platforms for ophthalmic drug delivery. This review summarizes the classification, fabrication strategies, and essential properties of hydrogels, and highlights recent advances in their application to ocular diseases, including keratitis management, corneal wound repair, intraocular pressure regulation and neuroprotection in glaucoma, sustained drug delivery for AMD and DR, vitreous substitutes for retinal detachment, and therapies for DED. In particular, we highlight recent advances in stimuli-responsive hydrogels that enable spatiotemporally controlled drug release in response to ocular cues such as temperature, pH, redox state, and enzyme activity, thereby enhancing therapeutic precision and efficacy. Furthermore, this review critically evaluates translational aspects, including long-term ocular safety, clinical feasibility, manufacturing scalability, and regulatory challenges, which are often underrepresented in existing reviews. By integrating material science, ocular pathology, and translational considerations, this review aims to provide a comprehensive framework for the rational design of next-generation hydrogel systems and to facilitate their clinical translation in ophthalmic therapy. Full article

Background and Clinical Significance: Radiation-induced lumbosacral plexopathy (RILP) is a rare but potentially debilitating complication of radiotherapy, typically affecting patients treated for pelvic malignancies. We report the first documented case of asymmetric RILP following radiotherapy for breast cancer. Case Presentation: A 64-year-old woman developed progressive left lower limb weakness, foot drop, and sensory disturbances four years after receiving locoregional radiotherapy extending to the left thoracoabdominal and lumbar areas. Electrophysiological studies revealed an asymmetric sensorimotor axonal neuropathy predominantly involving the left lower limb, without conduction block and sparing the upper limbs, whereas needle electromyography of the lower limbs showed fibrillation potentials, positive sharp waves, and fasciculations in the vastus lateralis, tibialis anterior, and medial gastrocnemius muscles on the left. Magnetic resonance imaging demonstrated edema and contrast enhancement of bilateral L2–L4 nerve roots with paraspinal muscle atrophy. Cerebrospinal fluid analysis showed albuminocytologic dissociation and elevated neurofilament levels. After exclusion of alternative diagnoses, including amyotrophic lateral sclerosis and inflammatory neuropathies, a diagnosis of radiation-induced peripheral neuropathy and RILP was made. The patient’s condition stabilized with physiotherapy and symptomatic treatment. Conclusions: This case highlights the need for heightened awareness of RILP as a late complication of breast cancer radiotherapy, underscoring the importance of accurate diagnosis to avoid misclassification and unnecessary treatments. Clinicians should carefully integrate all clinical elements—including a thorough remote medical history—since radiation-related neurological damage may manifest many years after the initial insult. Full article

Recent breakthroughs in materials science have driven transformative advancements in restorative dentistry. Advanced dental materials, such as bioactive materials, nanocomposites, and fibre-reinforced composites, are attracting attention. Bioactive materials, such as calcium silicate-based cements and bioactive glass, represent a paradigm shift by interacting with biological tissues to stimulate regeneration. They promote hydroxyapatite formation, accelerating mineralisation in hard and soft tissues, and are pivotal tools in minimally invasive procedures due to their functions of structural support and biological interaction. Nanomaterials, especially nanocomposites with embedded nanoparticles, effectively address polymerisation shrinkage and wear in traditional composites. With just 1.5% shrinkage, a flexural strength over 150 MPa, and 44–60% higher wear resistance than conventional composites, they offer significant improvements. Nanocomposites also provide enamel-like translucency and a bond strength of 27–38 MPa to dentin, ensuring excellent aesthetics and durability—making them ideal for direct restorations. Fibre-reinforced composites with glass or polymer fibres balance aesthetics with strength and are increasingly used in restorations. Their high fracture resistance, which closely approaches that of a natural tooth, enables clinicians to preserve more healthy teeth during restoration, in line with the principles of modern conservative dentistry. Overall, bioactive materials enhance tissue repair, nanocomposites optimise form and function, and fibre-reinforced composites deliver strength without compromising aesthetics. As these materials transition from research to clinical practice, they promise longer-lasting treatments, fewer complications, and higher patient satisfaction. This narrative review aims to explore three types of advanced dental materials and their role in improving clinical outcomes. Full article

Prostate cancer (PCa) is the most common malignancy in men, characterized by significant genetic and epigenetic heterogeneity, which complicates both diagnosis and treatment processes. Epigenetic mechanisms—including DNA methylation, chromatin remodeling, and dysregulated non-coding RNAs (miRNAs, lncRNAs, circRNAs)—contribute to tumor initiation, progression, and therapy resistance, offering promising diagnostic and prognostic biomarker opportunities. Liquid biopsy technologies, such as circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and exosomes, allow minimally invasive, real-time monitoring of tumor evolution and resistance mechanisms, complementing traditional biomarkers like PSA and supporting precision oncology approaches. Clinically implemented assays, including PCA3, ConfirmMDx, and ExoDx Prostate, along with emerging multi-analyte panels, enhance risk stratification, reduce unnecessary biopsies, and guide therapeutic decisions. Integration of epigenetic and liquid biopsy biomarkers into multimodal diagnostic pathways has the potential to support personalized management of prostate cancer; however, many still require further validation and optimization. Full article

Background: Intraventricular tumors represent a minority in the context of brain tumors, but their surgical treatment is particularly complex due to their vascularization and visualization, especially in deep localization. The characteristics of these tumors make them ideal candidates for minimally invasive surgical strategies such as the tubular retractor technique, above all in the elderly population. Objectives: A 1-year multi-center, retrospective case series was performed: the authors describe their preliminary experience using a neuronavigated tubular retractor in the management of 11 cases of intraventricular meningiomas. Methods: Clinical and radiological findings were examined to define the outcomes. We used an alternative tubular retractor system obtained using a modified preexisting general surgery trocar (ENDOPATH XCEL 15 mm trocar) or the NICO System BrainPath. Results: Gross total resection, defined as the removal of all the tumor visible from the brain scans, was achieved in all cases. Ten out of eleven of the patients did not experience major complications or permanent neurological deficits. Four patients presented transitory post-operative agitation, visual blurring and transient hemiparesis. All patients (mean age 72.6 years) were discharged from the hospital in 5–7 days. Conclusions: Our preliminary experience suggests that the use of navigated tubular retractors, by displacing the fibers and hence minimizing the damage to the surrounding cerebral parenchyma, is feasible and safe, representing a minimally invasive technique for a personalized and patient-tailored approach. The use of the selective ultrasonic aspirator makes it possible to excise the tumor through the narrow corridor of the tubular lumen of around 2 cm, and this technique can also be improved using both endoscope and microscope guidance. Full article

Background/Objectives: Implant-supported rehabilitations using the All-on-4 concept represent a viable treatment option for completely edentulous patients. The guided surgery software allows for the performance of a flapless computer-guided surgery with similar results to those achieved through a flap surgery. This study aimed to evaluate the long-term outcomes of complete edentulous implant-supported rehabilitations using an All-on-4 arrangement, following a computer-guided protocol. Methods: A total of 111 patients (68 females, 43 males) with an average age of 60.9 years ± 9.67 years were treated. The primary outcome measures were implant and prosthetic survival. Secondary outcome measures were marginal bone loss (MBL) and the incidence of mechanical and biological complications. Results: Thirty-nine patients were lost to follow-up. Thirty-seven implants and five prostheses failed, rendering a 92.5% implant cumulative survival rate and a 96.2% prosthetic survival rate at 12 years. The average MBL per implant was 1.19 ± 1.16 mm, with 1.26 ± 1.33 mm for axial implants and 1.12 ± 0.95 mm for tilted implants at 10 years. The incidence rate of mechanical complications at the patient level was 90.1% for provisional prostheses and 55.9% for definitive prostheses. The rate of biological complications was 14.3% at the implant level. Conclusions: Full-arch rehabilitations following an All-on-4 implant arrangement and assisted by a computer-guided protocol may be a viable alternative for patients with edentulism/hopeless teeth in the long term. Full article

The management of lung cancer (LC) in patients with interstitial lung diseases (ILDs) presents significant challenges, particularly with the increasing use of immunotherapy (IT). Immunotherapy-related pneumonitis (ICIP) is a potential complication of immune checkpoint inhibitors (ICIs) that can be difficult to differentiate from pre-existing or treatment-induced ILD. The incidence of treatment-related pneumonitis is higher in patients with pre-existing ILD, which complicates the therapeutic approach. Moreover, antifibrotic drugs have shown potential in reducing the incidence of post-operative acute exacerbations in IPF patients undergoing surgery and radiotherapy. ILDs in LC patients can either develop ab initio, linked to environmental exposures, autoimmune diseases, or emerge because of cancer therapies. Although large-scale clinical trial evidence remains limited, careful therapy selection, early detection of pneumonitis, and close monitoring are crucial. Further prospective studies are needed to refine therapeutic strategies, particularly regarding the role of IT in this sensitive population and the role of combination therapies with antifibrotics and ICIs to optimize outcomes for patients with both LC and ILDs. This review summarizes the available evidence on the safety and efficacy of IT in this population, emphasizing the importance of personalized treatment approaches and vigilant monitoring. Full article

Background/Objectives: Pleural mesothelioma (PM) frequently recurs despite multimodal therapy. Here, we aimed to retrospectively evaluate the safety and potential clinical benefit of radiofrequency ablation (RFA) for recurrent PM. Methods: Fourteen consecutive patients underwent CT-guided RFA between July 2019 and June 2025. The cohort comprised 13 men and 1 woman, with a median age of 69 (range, 54–77) years. All patients had previously received systemic therapy, and 12 had undergone surgery. Seven patients (50%) presented with multiple lesions, and 25 tumors (median diameter 1.8 cm; range, 0.5–7.0 cm) were treated in 23 sessions. Outcomes assessed were local tumor control, complications, and survival. Local progression and overall survival were estimated using Kaplan–Meier analysis. Adverse events were classified according to the Society of Interventional Radiology guidelines. Results: Technical success was achieved in all sessions. Two tumors showed local recurrence, corresponding to 1- and 2-year local progression rates of 10.6%. Seven patients showed distant metastases, most of whom subsequently received systemic therapy. Three patients died, two from disease progression and one from treatment-related gastrointestinal perforation during therapy for an unrelated cancer. The overall survival rates were 100%, 100%, and 60% at 1, 3, and 5 years, respectively. Major and minor complications occurred in one case each (4.3%): a refractory skin ulcer and retroperitoneal hematoma, respectively. Conclusions: RFA was technically feasible and generally well tolerated and helped achieve encouraging local control and survival in patients with recurrent PM, warranting further evaluation of RFA as a complementary approach in multimodal treatment strategies. Full article

Background/Objectives: Parent artery disease (PAD) is a significant yet often overlooked contributor to ischemic strokes, particularly affecting the perforating arteries. This study aims to evaluate the impact of PAD on endovascular treatment outcomes in patients with intracranial atherosclerosis. Methods: A narrative review was conducted, synthesizing the existing literature on PAD and its relationship with endovascular interventions. Key studies were analyzed to assess the effectiveness of imaging techniques like high-resolution Magnetic Resonance Imaging (MRI) and the implications of plaque morphology on treatment strategies. Results: The findings indicate that PAD significantly complicates endovascular procedures, often leading to perforating artery occlusions and increased rates of stroke recurrence. Patients with PAD-related strokes demonstrated larger lesion volumes and more severe neurological deficits compared to those with small vessel disease. The review highlights the challenges of accurately diagnosing PAD using conventional imaging techniques, emphasizing the need for advanced modalities to identify atheromatous plaques that may not cause significant stenosis. Conclusions: The study underscores the necessity for a shift in clinical practice towards recognizing and managing PAD in patients with ischemic strokes. Enhanced imaging techniques and tailored endovascular strategies are essential to improve patient outcomes and minimize the risk of recurrent strokes. Further research is needed to establish comprehensive guidelines for addressing PAD in acute stroke management. Full article

Background: Alveolar echinococcosis (AE) is a neglected parasitic disease caused by Echinococcus multilocularis that is difficult to diagnose and treat. Methods: This systematic review has gathered articles presenting original data from the past 5 years, from January 2020 to December 2025, with epidemiological data (incidence, prevalence), treatment options, case reports, and other findings relevant to the prevention and control of this disease, representing the inclusion criteria of this study. Three medical databases were searched for the study: PubMed, Web of Science, and ScienceDirect. To improve our understanding of the available data, no spatial or temporal restrictions were imposed on the study’s duration or follow-up period. Results: A total of 248 articles are included in this review, which describe atypical sites and complications owing to Echinococcus multilocularis infection, the heterogeneity of epidemiological studies in different endemic and non-endemic regions, diagnosis techniques based on imaging, histopathology, and molecular techniques, as well as surgical and non-surgical treatment options (and lack thereof regarding the latter). Conclusions: Although advances have been made in the diagnosis, management, and treatment of AE, challenges remain, particularly with regard to misdiagnosis, delayed diagnosis, and limited antiparasitic therapy. Full article

Intravenous thrombolysis with recombinant tissue-type plasminogen activator (tPA) remains a keystone of acute ischemic stroke treatment but in a subset of patients is complicated by angioedema, a potentially life-threatening adverse event largely mediated by bradykinin signaling. The unpredictable and idiosyncratic nature of this reaction has long suggested an underlying genetic contribution, yet its molecular architecture has remained poorly characterized. We hypothesized that alteplase-associated angioedema represents a multigenic susceptibility phenotype, arising from the convergence of rare genetic variants across multiple interacting physiological systems rather than from a single causal variant. To explore this hypothesis, we performed clinical exome sequencing in a cohort of 11 patients who developed angioedema following alteplase administration. Rather than identifying a shared pathogenic variant, we observed distinct yet convergent patterns of genetic vulnerability, allowing patients to be grouped according to dominant, but overlapping, biological axes. These included alterations affecting bradykinin regulation (e.g., ACE, SERPING1, XPNPEP2), endothelial structure and hemostasis (e.g., VWF, COL4A1), neurovascular and calcium signaling (e.g., SCN10A, RYR1), and vascular repair or remodeling pathways (e.g., PSEN2, BRCA2). Notably, many of the identified variants were classified as Variant of Uncertain Significance (VUS) or likely benign significance in isolation. However, when considered within an integrated, pathway-based framework, these variants can be interpreted as capable of contributing cumulatively to system level fragility, a phenomenon best described as “contextual pathogenicity”. Under the acute biochemical and proteolytic stress imposed by thrombolysis, this reduced physiological reserve may allow otherwise compensated vulnerabilities to become clinically manifest. Together, these findings support a model in which severe alteplase-associated angioedema appears as an emergent property of interacting genetic networks, rather than a monogenic disorder. This systems level perspective underscores the limitations of gene centric interpretation for adverse drug reactions and highlights the potential value of pathway informed, multi-genic approaches to risk stratification. Such frameworks may ultimately contribute to safer, more personalized thrombolytic decision, while providing a conceptual foundation for future functional and translational studies. Full article