Search Results (5,301)

Background/Objectives: Diabetic Foot Ulceration (DFU) is one of the most debilitating and costly complications of diabetes mellitus, representing a significant cause of morbidity, disability, and healthcare burden worldwide. Refractory non-healing ulcers that fail to respond to conventional therapies require novel adjuvant treatment modalities. This clinical audit aimed to evaluate the long-term clinical outcomes of an autologous, bioactive platelet-rich fibrin (PRF) matrix combined with topical gentamicin in patients with chronic, non-healing DFUs. Methods: A retrospective observational audit was conducted, involving eleven patients with refractory DFUs who underwent adjunctive treatment with a PRF matrix (Arthrozheal^®) and co-applied gentamicin. Patients were followed at three-week intervals using standardised wound imaging (Silhouette^® 3D) to assess healing parameters. Long-term follow-up data, evaluating healing durability and complications, is presented. Results: All patients completed the treatment protocol, with significant reductions in mean wound area (87.9%), perimeter, depth, and volume (all p < 0.05). Epithelialised tissue increased from 24.7% to 82.8%. At 12 months, 81.8% of patients maintained complete ulcer healing. Two patients experienced complications: one ulcer recurrence requiring surgical debridement and one unrelated amputation due to osteomyelitis. Conclusions: The combination of autologous PRF matrix and gentamicin demonstrated promising results in promoting sustained healing of refractory DFUs with minimal complications. These findings support further investigation in larger, controlled studies to validate this biologic-antimicrobial approach as a safe, effective, and durable therapy for complex diabetic wounds. Full article

Background: Juvenile idiopathic arthritis-associated uveitis (JIA-U) is a rare condition, and assessment of the efficacy of disease-modifying antirheumatic drugs, synthetic (sDMARD) or biological (bDMARD), in randomized trials is hindered by this fact. Methods: In this prospective longitudinal study, we observed 38 children aged 1.3 to 15.2 years, with 69 eyes affected with JIA-U for 1970 overall eye examinations (6–59, median 16) irregularly scattered across 4.4–87.6 months (median 21.6) of follow-up, with on- and off-periods of DMARD use and use of topical treatments. Results: With adjustment for several time-invariant and time-varying covariates, periods of exposure to sDMARD vs. no DMARD exposure were associated with peak benefits of 15–20% lower probability of having more severe anterior chamber (AC) inflammation and a similar relative reduction in the daily use of topical corticosteroids (TCS). Periods of bDMARD exposure or of bDMARD + sDMARD exposure vs. no DMARD use were associated with peak benefits of an around 50% reduction in the probability of having more severe AC inflammation, and peak benefits of an around 60–65% reduction in TCS use. Conclusions: The observations regarding bDMARD (only) or bDMARD + sDMARD exposure are in agreement with the extent of benefits suggested for adalimumab vs. placebo (+background sDMARD) in the only existing randomized trial in this setting evaluating AC inflammation and TCS use. Full article

Notalgia paresthetica is a condition characterized by pruritus and pain in the upper back, often associated with skin discoloration in the same area. Through Medline, Google Scholar, and Scopus search engines, we identified reports of eight clinical studies (published up to 1 December 2025) on the subject of botulinum neurotoxin therapy for Notalgia Paresthetica (NP). Only one of the eight studies was double-blind and placebo-controlled. The search strategy included only articles published in English and Spanish, and articles providing basic information such as the type of study, type and dose of the toxin, and results of the treatment. Articles not in English or Spanish, review articles, and articles failing basic information were excluded. A total of 34 patients were found across all studies. The injected toxin in the open-label studies was onabotulinumtoxin-A (Botox), whereas in the blinded study, the investigators used incobotulinumtoxinA (Xeomin). All open-label studies reported improvement in pruritus, and some reported improvement in pain, whereas the blinded study failed to do so. The possible reasons for this discrepancy between the blinded and the open-label studies are discussed. There is a need for double-blind, placebo-controlled studies with a larger number of patients, preferably using the same neurotoxin that has suggested efficacy in the open-label studies. The novelty of this review is that it represents a comprehensive and critical literature assessment on this topic and that it includes data not present in the previous reviews of this subject. Full article

Background/Objectives: Burning Mouth Syndrome (BMS) is a common oral condition in older women and is characterized by a multifactorial etiology. To date, no standardized treatment strategy has been established. The aim of this study was to evaluate the effectiveness of topical application of capsaicin (0.025 mg/cm²) in the form of a mucoadhesive bilayer polymer reducing burning sensations in BMS. The study assessed levels of depression, sleep disturbances, and quality of life. Material and Methods: The proof-of-concept study included 29 patients with symptoms of BMS. The peripheral origin of BMS was confirmed by lingual nerve block. Pain intensity was assessed using the Numeric Rating Scale (NRS-11) and the Short-Form McGill Pain Questionnaire (SF-MPQ). Depression, sleep disturbances, and quality of life were evaluated using the Beck Depression Inventory (BDI), Athens Insomnia Scale (AIS), and WHO Quality of Life Questionnaire (WHOQoL). Results: A reduction in pain was observed in over 86% patients. Decrease in burning at treatment sites was recorded immediately after treatment and also at the 3-month follow-up. Gender, taste disturbances, depression, and age were found to have a significant effect on final NRS-11 scores. Conclusions: Significant reduction in pain intensity was achieved in nearly all treated patients, with adverse effects being rare. Full article

Microbial resistance to antibiotics necessitates the development of alternative treatments to address the challenges posed by severe bacterial infections. Bacteriophages are regaining clinical relevance, but the effectiveness of phage therapy depends directly on the route of administration and the carrier used. This review provides a critical overview of the therapeutic potential of phages, emphasizing different strategies for delivery to the site of infection. We focus on the preclinical and clinical data on phage therapies using various routes of administration, such as oral, intravenous, inhalation, topical, and local administration to joints and bones. In view of different phage formulations, including liquid suspension, phages immobilized in polymers or liposome-based carriers, we highlight the potential challenges and obstacles that may affect phage stability and bioavailability and limit the successful outcome of therapy. This review serves to enhance the understanding of the integration of materials engineering with clinical practice and production standardization, to address these issues. Additionally, a clear knowledge of the bacteriophage and pharmacokinetics of phage preparations is necessary to implement safe and efficacious bacteriophage treatment in the era of antimicrobial resistance. Full article

Cataracts remain the leading cause of blindness worldwide, and surgery is currently the only effective clinical treatment, as no pharmacological therapy has yet been validated. Here, we explore Fullerenol, a hydroxylated fullerene derivative formulated as eye drops, as a potential nanomedicine for delaying cataract onset and progression. In UVB-induced mouse cataract models, topical Fullerenol preserved the lens transparency and histological structure. In human lens epithelial cells, Fullerenol reduced the oxidative stress, restored the mitochondrial function, alleviated the DNA damage, and suppressed the cellular senescence. RNA sequencing and pathway enrichment analyses further indicated that Fullerenol modulated the oxidative stress- and senescence-associated signaling pathways, including MAPK and TGF-β cascades, while downregulating the p53–CDKN1A (p21) axis. These findings provide new evidence that Fullerenol can mitigate photo-oxidative damage and age-related cellular dysfunction, highlighting its promise as a non-invasive and clinically translatable nanomedicine strategy for cataract management. Full article

Lignocellulosic bio-based materials, such as wood, biocomposites, and natural fibers, exhibit desirable structural properties. This comprehensive review emphasizes the foundational and latest advancements in bioinspired improvement strategies, such as direct mineralization, biomineralization, lignocellulosic nanomaterials, protein-based treatments, and metal-chelating processes. Significant focus was placed on biomimetics, emulating natural protective mechanisms, with discussions on relevant topics including hierarchical mineral deposition, free-radical formation and quenching, and selective metal ion binding, and relating them to lignocellulosic bio-based material property improvements, particularly against fire and fungi. This review evaluates the effectiveness of different bioinspired processes: mineralized and biomineralized composites improve thermal stability, nanocellulose and lignin nanoparticles provide physical, thermal, and chemical barriers, proteins offer biochemical inhibition and mineral templating, and chelators interfere with fungal oxidative pathways while simultaneously improving fire retardancy through selective binding with metal ions. Synergistic approaches integrating various mechanisms could potentially lead to long-lasting and multifunctional protection. This review also highlights the research gaps, challenges, and potential for future applications. Full article

Background: This study aimed to identify the baseline characteristics predictive of Psoriasis Area and Sensitivity Index (PASI) 90 response to guselkumab and assess treatment effectiveness outcomes for PASI 90 responders and PASI 90 non-responders. Methods: This post hoc analysis used data from a prospective, multicenter, observational study of guselkumab in Korean patients with moderate-to-severe psoriasis conducted between February 2019 and March 2022. Stepwise logistic regression analysis was used to identify baseline characteristics predictive of PASI 90 response. Results: Of 339 patients, 245 (72.3%) week-28 PASI 90 responders and 94 (27.7%) non-responders were identified. Baseline characteristics significantly predictive of PASI 90 response in multivariate logistic regression were absence of family history of psoriasis (odds ratio [OR]: 0.35; p = 0.0266), higher PASI score (OR: 1.22; p = 0.0006), higher body surface area of psoriasis involvement (OR: 0.95; p = 0.0127), prior phototherapy use (OR: 2.44; p = 0.0108), and reduced concomitant topical agent use (OR: 0.41; p = 0.0044). More PASI 90 responders versus non-responders achieved absolute PASI score ≤ 2 by week 44 (95.8% vs. 67.5%) and Dermatology Life Quality Index scores of 0 or 1 by week 28 (72.2% vs. 34.0%). Conclusions: Guselkumab PASI 90 responders had unique baseline characteristics that may predict positive treatment outcomes. Full article

Skin cancer is among the most common malignancies worldwide, posing a significant societal burden due to its increasing incidence and its limited responsiveness to conventional topical therapies. Treatment is challenged by the presence of the skin barrier which restricts drug penetration. This review discusses the structural and physiological challenges of topical delivery and summarizes efforts to develop functional biomaterials to enhance skin drug penetration. Important aspects to consider when developing formulation strategies, such as drug properties and release mechanisms, are discussed alongside current limitations and future perspectives. Full article

Background/Objectives: Hypopigmented mycosis fungoides (hMF) is a rare variant of mycosis fungoides (MF) often seen in younger patients and individuals with darker skin phototypes. The lesions develop as hypopigmented patches or plaques, and they are usually asymptomatic and respond well to topical treatment or phototherapy. Methods: We provide a systematic review on hMF with onset at or beyond 30 years of age, based on SCOPUS, PubMed, and Embase databases. A total of 13 original articles, totaling 34 patients, were included in this review. Evidence was limited to case reports and small series; PROSPERO registration is CRD420251181894. Results: The majority of cases did not progress beyond stage IB and commonly used treatment methods, including topical corticosteroids and phototherapy. In three patients, a progression of the disease occurred, and in two of them it was fetal. Among patients receiving phototherapy, PUVA therapy achieved complete remission more often than UVB (13 out of 17 cases vs. 8 out of 16 cases). Although recurrences occurred with both treatments, they were less frequent, and relapses took longer to develop in the PUVA group. Conclusions: In this cohort, PUVA appeared to be associated with higher complete response rates and longer remission duration than UVB. However, this advantage of PUVA is derived from low-level evidence and should be confirmed in prospective comparative studies. Full article

Extracting and organizing knowledge from the agricultural crop disease research literature are challenging tasks because of the heterogeneous terminologies, complicated symptom descriptions, and unstructured nature of scientific documents. In this study, we developed a multi-stage natural language processing (NLP) pipeline to automate knowledge extraction, organization, and integration from the agricultural research literature into a domain-consistent crop disease knowledge graph. The model combines transformer-based sentence embeddings with variational deep clustering to extract topics, which are further refined via facet-aware relevance scoring for sentence selection to be included in the summary. Lexicon-guided named entity recognition helps in the precise identification and normalization of terms for crops, diseases, symptoms, etc. Relation extraction based on a combination of lexical, semantic, and contextual features leads to the meaningful generation of triplets for the knowledge graph. The experimental results show that the method yielded consistently good results at each stage of the knowledge extraction process. Among the combinations of embedding and deep clustering methods, SciBERT + VaDE achieved the best clustering results. The extraction of representative sentences for disease symptoms, control/treatment, and prevention obtained high F1-scores of around 0.8. The resulting knowledge graph has high node coverage and high relation completeness, as well as high precision and recall in triplet generation. The multi-stage NLP pipeline effectively converts unstructured agricultural research texts into a coherent and semantically rich knowledge graph, providing a basis for further research in crop disease analysis, knowledge retrieval, and data-driven decision support in agricultural informatics. Full article

Objective: To evaluate treatment patterns, predictors of treatment selection, and overall survival (OS) in patients with noninvasive (Ta–Tis) urothelial carcinoma of the urethra (UUC). Patients and Methods: We conducted a retrospective cohort study of adults diagnosed with noninvasive UUC (stage Ta or Tis, N0, M0) between 2018 and 2021 using the National Cancer Database. Patients were categorized into prostatic and non-prostatic urethral cohorts. Treatment groups included endoluminal ablation alone, ablation combined with topical intraluminal therapy, urethrectomy, and no subsequent treatment. Multinomial logistic regression was used to identify predictors of treatment selection. The OS was assessed using Kaplan–Meier and multivariable Cox regression, with separate models for each anatomical cohort. Results: A total of 436 patients were included (185 non-prostatic, 251 prostatic); 91.9% (n = 401) were male. Ablation alone was the most common treatment in both cohorts (non-prostatic: 57.3%; prostatic: 62.6%), followed by urethrectomy (non-prostatic: 21.1%) and ablation plus topical therapy (prostatic: 20.3%). In the non-prostatic cohort, high-grade histology (OR 15.15; 95% CI, 3.82–60.04) and Tis stage (OR 3.27; 95% CI, 1.10–9.69) were associated with increased odds of urethrectomy. In the prostatic cohort, high-grade histology was associated with increased use of urethrectomy (OR 59.29; 95% CI, 4.61–763.17) and ablation plus topical therapy (OR 3.09; 95% CI, 1.21–7.90). Tis stage was also associated with ablation plus topical therapy (OR 2.53; 95% CI, 1.14–5.62). This treatment approach was associated with improved OS compared with ablation alone (HR 0.18; 95% CI, 0.05–0.60; p = 0.005). Conclusions: Treatment selection differed substantially by tumor location, stage, and grade, reflecting both treatment selection in noninvasive UUC varied by tumor location, grade, and stage. In prostatic tumors, ablation plus topical therapy was associated with improved survival, supporting its role as a risk-adapted, organ-sparing strategy in selected patients. Full article

Pseudomonas aeruginosa is a resilient Gram-negative pathogen frequently implicated in healthcare associated infections, particularly among immunocompromised individuals and those with chronic conditions such as cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD), or cancer. It is well known for its high resistance to antibiotic treatment. This review briefly mentions P. aeruginosa’s resistance mechanisms, biofilm formation, and virulence factors, while primarily focusing on treatment challenges and recent advancements in therapeutic strategies aimed at overcoming resistance. Covered are novel non-antibiotic interventions such as quorum sensing inhibitors, quorum quenching agents, iron chelators, lectin and efflux pump inhibitors, as well as antimicrobial peptides and nanoparticles. Traditional medicine, phytochemicals, and probiotics are also evaluated. Additionally, this review explores the development of a viable vaccine, bacteriophage therapy, lactoferrin-hypothiocyanite combination, and topical use of electrochemical scaffolds. This review emphasizes the need for extensive safety studies and in vivo validation of these emerging non-antibiotic therapeutic strategies to determine their efficacy, pharmacological behavior, and clinical feasibility before they can be translated into practice. Many of these emerging treatments could play a vital role in future combination therapies by enhancing the efficacy of existing antibiotics and countering resistance and virulence mechanisms. Advancing these approaches from laboratory to clinical application remains a major challenge, making the development of approved therapies or vaccines a critical scientific and public health priority. Full article

The cornea is an avascular, immune-privileged tissue critical to maintaining transparency, optimal light refraction, and protection from microbial and immunogenic insults. Corneal neovascularization (CoNV) is a pathological sequela of multiple anterior segment diseases and presents a major cause for reduced visual acuity and overall quality of life. Various aetiologies, including infection (e.g., herpes simplex), inflammation (e.g., infective keratitis), hypoxia (e.g., contact lens overuse), degeneration (e.g., chemical burns), and trauma, disrupt the homeostatic avascular microenvironment, triggering an overactive compensatory response. This response is governed by a complex interplay of pro- and anti-angiogenic factors. This review investigates the potential for these mediators to serve as therapeutic targets. Current therapeutic strategies for CoNV encompass topical corticosteroids, anti-VEGF injections, fine-needle diathermy, and laser modalities including argon, photodynamic therapy and Nd:YAG. Emerging therapies involve steroid-sparing immunosuppressants (including cyclosporine and rapamycin), anti-fibrotic agents and advanced drug delivery systems, including ocular nanosystems and viral vectors, to enhance drug bioavailability. Adjunctive therapy to attenuate the protective corneal epithelium prior to target neovascular plexi are further explored. Gene-based approaches, such as Aganirsen (antisense oligonucleotides) and CRISPR/Cas9-mediated VEGF-A editing, have shown promise in preclinical studies for CoNV regression and remission. Given the multifactorial pathophysiology of CoNV, combination therapies targeting multiple molecular pathways may offer improved visual outcomes. Case studies of CoNV highlight the need for multifaceted approaches tailored to patient demographics and underlying ocular diseases. Future research and clinical trials are essential to elucidate optimal therapeutic strategies and explore combination therapies to ensure better management, improved treatment outcomes, and long-term remission of this visually disabling condition. Full article

Transanal Irrigation (TAI) and Colon Hydrotherapy (CHT) represent emerging therapeutic options that may complement first-line interventions or serve as rescue treatments for chronic constipation and fecal incontinence. Their clinical utility depends on patient characteristics, specific therapeutic goals, device features, and probe type, as well as the procedural setting. This review presents the various pathophysiological contexts in which these techniques can be applied, analyzing their specific characteristics and potential pros and cons. Moreover, these interventions are also considered within a Psycho-Neuro-Endocrino-Immunological (PNEI) framework, given the potential influence of intestinal function and microbiota modulation on the bidirectional communication pathways linking the enteric nervous system, neuroendocrine regulation, immune activity, and global patient well-being. Since there is not yet enough scientific data on this topic, future research should prioritize randomized controlled trials comparing these techniques with other standard treatments (e.g., laxatives or dietary fiber) in defined patient populations. Longitudinal studies will also be essential to clarify long-term safety, potential effects on microbiota, and both risks and benefits. Standardization of technical procedures also remains a critical need, especially regarding professional competencies, operating parameters (e.g., instilled volumes and pressure ranges), and reproducible protocols. Moreover, future investigations should incorporate objective outcome measures, as colonic transit time, stool form and frequency, indices of inflammation or intestinal wall integrity, and changes to microbiome composition. In conclusion, TAI and CHT have the potential to serve as important interventions for the treatment and prevention of chronic constipation and intestinal dysbiosis, as well as their broader systemic correlates, in the setting of bio-integrated medicine. Full article