Search Results (1,831)

Background: Aloe vera gel in 0.3% hyaluronate (AV/HA) could mitigate glaucoma therapy-related ocular surface disease (GTOSD). Methods: Thirty-nine patients diagnosed with GTOSD and receiving AV/HA or HA underwent ocular surface disease index (OSDI), Symptom Assessment iN Dry Eye (SANDE), National Eye Institute Visual Function Questionnaire (NEI VFQ)-25 questionnaires, and tear matrix metalloproteinase-9 (MMP-9), break-up time (BUT), corneal fluorescein staining (CFS), Schirmer test I (STI), and bulbar conjunctival hyperemia (BCH) determination. Results: After one month, AV/HA increased BUT (5 (7–4.5) to 7 (8–5.5)) and STI (12 (19.5–8) to 13.5 (20–10)), while it decreased BCH (2.2 (2.3–1.3) to 2.1 (2.2–1.2)) and CFS (3 (4–2) to 2 (3.0–1.5)) (p < 0.001). SANDE and OSDI scores were reduced from 36.18 (38.5–20.5) to 22.91 (31.5–17.21), and 29.5 (32.5–19.5) to 20 (26.5–18) (p < 0.001). HA reduced BCH from 2.75 (3.20–2.15) to 2.25 (2.30–1.90) (p = 0.014) and CFS from 3.5 (5–2.75) to 2.5 (4–2) (p = 0.014), while it increased BUT (p = 0.036). The SANDE score decreased from 28.95 (47.6–20.9) to 26.86 (36.41–19.90) (p = 0.009), whereas the OSDI decreased from 40 (49–19.5) to 29 (42–19.75) (p = 0.005). Any significant change in NEI VFQ-25 was collected. A trend for an MMP-9 immunoassay positivity reduction was observed in AV/HA (0.073). Conclusions: These findings invite considering lubricants enriched with natural anti-inflammatory agents, such as Aloe vera, as a potential adjunctive option to improve the ocular surface in glaucoma. Full article

Hard-to-heal wounds remain a significant challenge for healthcare professionals, particularly in aging populations. Although most chronic wounds are associated with diabetes or chronic venous insufficiency, rare etiologies should also be considered. One such cause is envenomation by Phoneutria spp. (native to South America, rare in Europe). Their venom contains potent neurotoxins. While systemic manifestations are more commonly reported, localized necrotic skin lesions may also occur. This case report presents a rare chronic wound following a suspected Phoneutria spider bite and highlights the importance of an individualized, multimodal treatment approach. A 61-year-old male patient with a progressive thigh wound following a spider bite sustained during work. Despite initial self-treatment and pharmacotherapy the wound deteriorated. The patient was admitted to the authors’ facility, where surgical treatment included necrosectomy and a sandwich graft using an acellular dermal matrix combined with a split-thickness skin graft. Adjunctive therapies included negative pressure wound therapy and hyperbaric oxygen therapy. After discharge, outpatient wound care was continued. Treatment was monitored with photographic documentation and serial microperfusion measurements. Complete wound closure was achieved after 4 months of specialized therapy. Management of chronic wounds requires a multidisciplinary and individualized approach with surgical intervention, advanced wound care and specialized outpatient follow-up. Full article

Objective: This umbrella review aimed to synthesize evidence from meta-analyses on the efficacy of rebamipide in major gastrointestinal disorders and dyspeptic symptoms. Methods: This umbrella review followed Joanna Briggs Institute standards and was registered in PROSPERO (CRD420251185686). A comprehensive search of MEDLINE, EMBASE, Cochrane, and Scopus (1 January 1985, to 10 September 2025) was conducted to identify systematic reviews and meta-analyses assessing rebamipide therapy. Methodological quality was appraised using AMSTAR-2, ROBIS, and GRADE tools. Pooled data were analyzed using fixed- or random-effects models according to heterogeneity, as assessed using the I² statistic. Results: Eleven meta-analyses (88 primary studies) were included. Rebamipide significantly improved H. pylori eradication (OR = 1.76; 95% CI: 1.44–2.16), reduced NSAID-induced mucosal injury (OR = 2.72; 95% CI: 1.89–5.14), enhanced ulcer healing after endoscopic submucosal dissection (OR = 2.28; 95% CI: 1.42–3.65), and alleviated dyspeptic symptoms (OR = 2.95; 95% CI: 1.04–8.37). Overall evidence quality was moderate to high, with low to moderate risk of bias. Conclusions: Rebamipide demonstrates consistent therapeutic benefits across diverse gastrointestinal disorders, improving H. pylori eradication rates, mucosal protection, ulcer healing, and symptom relief. These findings support rebamipide as an effective and well-tolerated adjunctive agent for the prevention and management of upper gastrointestinal diseases. Full article

Background/Objectives: Cancer-associated fibroblasts (CAFs) are key stromal mediators of breast tumor progression and therapy resistance. Carvacrol, a dietary monoterpenic phenol, exhibits antiproliferative activity in cancer cells, but its effects on primary human breast CAFs remain unclear. This study aimed to determine whether carvacrol selectively induces mitochondria-related apoptotic signaling in breast CAFs while sparing normal fibroblasts (NFs). Methods: Primary fibroblast cultures were established from invasive ductal carcinoma tissues (CAFs, n = 9) and nonmalignant breast tissues (NFs, n = 5) and validated by α-SMA and FAP immunofluorescence. Cells were exposed to 400 μM carvacrol. Apoptosis was assessed by TUNEL assay and BAX/BCL-XL Western blotting. Changes in signaling pathways were evaluated by analyzing PPARα/NF-κB, sirtuin (SIRT1, SIRT3), autophagy-related markers (LAMP2A, p62), and matrix metalloproteinases (MMP-2, MMP-3). In silico molecular docking and 100-ns molecular dynamics simulations were performed to examine interactions between carvacrol and caspase-3 and caspase-9. Results: Carvacrol induced a pronounced, time-dependent apoptotic response in CAFs, with TUNEL-based viability declining to approximately 10% of control levels by 12 h and a marked increase in the BAX/BCL-XL ratio. In contrast, NFs exhibited minimal TUNEL positivity and no significant change in BAX/BCL-XL. In CAFs, but not NFs, carvacrol reduced PPARα expression and NF-κB nuclear localization, increased SIRT1 and SIRT3 levels, selectively suppressed MMP-3 while partially normalizing MMP-2, and altered autophagy-related markers (decreased LAMP2A and accumulation of p62), consistent with autophagic stress and possible impairment of autophagic flux. Computational analyses revealed stable carvacrol binding to caspase-3 and caspase-9 with modest stabilization of active-site loops, supporting caspase-dependent, mitochondria-related apoptosis. Conclusions: Carvacrol selectively targets breast cancer-associated fibroblasts by inducing mitochondria-related apoptotic signaling while largely sparing normal fibroblasts. This effect is accompanied by coordinated modulation of PPARα/NF-κB, sirtuin, autophagy, and MMP pathways. These findings support further evaluation of carvacrol as a microenvironment-directed adjunct in breast cancer therapy. Full article

Hair loss disorders, particularly androgenetic alopecia (AGA), are common conditions that carry significant psychosocial impact. Current standard therapies, including minoxidil, finasteride, and hair transplantation, primarily slow progression or re-distribute existing follicles and do not regenerate lost follicular structures. In recent years, regenerative medicine has been associated with a gradual shift toward approaches that aim to restore follicular function and architecture. Stem cell-derived conditioned media and exosomes have shown the ability to activate Wnt/β-catenin signaling, enhance angiogenesis, modulate inflammation, and promote dermal papilla cell survival, resulting in improved hair density and shaft thickness with favorable safety profiles. Autologous cell-based therapies, including adipose-derived stem cells and dermal sheath cup cells, have demonstrated the potential to rescue miniaturized follicles, although durability and standardization remain challenges. Adjunctive interventions such as microneedling and platelet-rich plasma (PRP) further augment follicular regeneration by inducing controlled micro-injury and releasing growth and neurotrophic factors. In parallel, machine learning-based diagnostic tools and deep hair phenotyping offer improved severity scoring, treatment monitoring, and personalized therapeutic planning, while robotic Follicular Unit Excision (FUE) platforms enhance surgical precision and graft preservation. Advances in tissue engineering and 3D follicle organoid culture suggest progress toward producing transplantable follicle units, though large-scale clinical translation is still in early development. Collectively, these emerging biological and technological strategies indicate movement beyond symptomatic management toward more targeted, multimodal approaches. Future progress will depend on standardized protocols, regulatory clarity, and long-term clinical trials to define which regenerative approaches can reliably achieve sustainable follicle renewal in routine cosmetic dermatology practice. Full article

Background/Objectives. Chronic benzodiazepine (BDZ) use is frequently maintained beyond recommended durations due to neuroadaptation, psychological dependence, and withdrawal-related issues. Passiflora incarnata L., herba (P. incarnata) has shown anxiolytic and GABAergic activity that may mitigate withdrawal symptoms, while cognitive-behavioural therapy (CBT) targets maladaptive beliefs and behaviours sustaining BDZ misuse. This study investigates the independent and interactive effects of P. incarnata and CBT on BDZ dose reduction during a three-month tapering program. Methods. This retrospective observational study included 186 outpatients with anxiety or depressive disorders in clinical remission undergoing BDZ tapering, of whom 93 received a dry extract of P. incarnata as adjunctive treatment and 93, matched for diagnosis, age and sex, followed a standard tapering protocol. BDZ doses were assessed at baseline and three months. CBT was recorded as a binary variable based on the information documented in the medical records. An ANCOVA was performed to assess the impact of CBT and P. incarnata on BDZ reduction (change in mg diazepam equivalents), adjusting for sex, age, education, baseline anxiety and depression scores, initial BDZ and antidepressant dosage. A subgroup analysis was conducted to investigate the role of P. incarnata dosage in BDZ reduction. Results. Both CBT and P. incarnata were associated with significantly greater reductions in BDZ dosage at three months (CBT: p = 0.005, effect size: 0.032; P. incarnata: p < 0.001, effect size: 0.128). A significant interaction between CBT and P. incarnata was also observed (p = 0.037, effect size: 0.018), indicating a synergistic effect when both interventions were combined. Baseline sociodemographic characteristics, BDZ and antidepressant dosage and symptom severity did not differ significantly between groups. Patients taking 400–600 mg of P. incarnata dry extract showed a higher BDZ reduction compared to those taking 200 mg. Conclusions. These findings suggest that P. incarnata and CBT exert independent yet complementary effects in supporting BDZ tapering. Their combination appears to enhance dose reduction beyond either intervention alone, supporting a multimodal approach that addresses both neurobiological and psychological components of BDZ addiction. Prospective controlled studies are needed to confirm these results and to clarify their impact on long-term discontinuation outcomes. Full article

Background: The microbiological landscape and infection-source profiles of severe sepsis in Asian ICUs differ markedly from Western cohorts and may influence the effectiveness and prognosis of adjunctive therapies such as polymyxin B hemoperfusion (PMX-HP). However, real-world data on how pathogen categories, multidrug resistance (MDR), and infection sources affect outcomes in PMX-HP-treated patients are lacking. Methods: We conducted a retrospective cohort study in a tertiary medical ICU in Taiwan, including adult patients with severe sepsis or septic shock who received PMX-HP between 2013 and 2019. Microbiological data, infection sources, MDR profiles, organ support requirements, vasoactive–inotropic score (VIS), and mortality outcomes were retrieved from electronic records. Pathogen groups (Gram-negative, Gram-positive, fungal, no-growth), MDR status, and infection sources were analyzed for associations with 28-day, ICU, and hospital mortality. Results: Among 64 patients (mean age 66.1 years; 67.2% male), Gram-negative pathogens predominated (70.3%), with Escherichia coli (31.3%) and Klebsiella pneumoniae (21.9%) being the most frequently identified organisms. MDR organisms were isolated in 26.6% of patients. The most common infection sources were pneumonia (29.7%), intra-abdominal infection (18.8%), and urinary tract infection (17.2%). Gram-negative infections were associated with higher CRRT utilization (71.9% vs. 47.1%, p = 0.04) and higher VIS at 24 h. MDR status was significantly associated with early CRRT requirement (64.7% vs. 38.6%, p = 0.048), but not with 28-day mortality (52.9% vs. 43.2%, p = 0.42). No infection source was independently associated with mortality after adjustment for APACHE II, CRRT, and VIS. Instead, greater organ failure severity—particularly renal failure requiring CRRT—was strongly associated with mortality in this cohort. Conclusions: In PMX-HP-treated severe sepsis patients, Gram-negative predominance and MDR status were associated with increased organ support requirements but were not independently associated with mortality. Outcomes were primarily associated with overall illness severity rather than microbiological category. These findings highlight the importance of combining microbiological data with dynamic physiological markers for prognostic risk stratification in Asian ICUs. 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

Background: Peri-implantitis, a condition characterized by inflammation and progressive bone loss around dental implants, presents a significant challenge in contemporary dentistry. Conventional non-surgical treatments often fail to fully eliminate bacterial biofilms, particularly on complex implant surfaces. Laser therapies have emerged as potential adjuncts due to their antimicrobial and bio-modulatory properties. However, their microbiological effectiveness and suitability for individualized patient treatment planning remain unclear. Objective: Τhis study aims to systematically assess and synthesize the microbiological effects of various laser-assisted non-surgical treatments for peri-implantitis compared to conventional mechanical debridement. Methods: This systematic review and meta-analysis followed PRISMA guidelines and was registered in PROSPERO (CRD420251035354). Randomized controlled trials (RCTs) evaluating microbiological changes following laser-assisted non-surgical treatment of peri-implantitis, with a minimum follow-up of one month, were identified through searches in multiple databases and registries up to February 2025. The ncluded studies used lasers such as diode, Er: YAG, and photodynamic therapy (PDT) either alone or as adjuncts to mechanical debridement. Outcomes of interest included bacterial counts. Risk of bias was assessed using the RoB2 tool, and certainty of evidence was evaluated via GRADE. Quantitative synthesis used random-effects meta-analysis, with standardized mean differences (SMDs) calculated. Results: Eight RCTs involving 266 patients and 335 implants were included in the systematic review. Quantitative synthesis of three pathogens (counts of Fusobacterium nucleatum, P. gingivalis, T. denticola) across three studies displayed no statistically significant differences between laser and control groups at 3 and 6 months (p > 0.05 for all comparisons). When examining individual study findings, PDT, particularly in patients with diabetes or acute abscess, showed short-term reductions in red complex bacteria (e.g., Porphyromonas gingivalis and Treponema denticola). In contrast, diode and Er: YAG lasers demonstrated inconsistent or transient effects. The quality of evidence was rated as very low according to GRADE. Conclusions: Laser-assisted therapies, especially PDT, may provide targeted microbiological benefit in selected patient groups, supporting their adjunctive use within personalized treatment planning rather than as replacements for mechanical debridement, which remains the gold standard. Further high-quality RCTs incorporating well-defined patient risk profiles, such as systemic conditions and behavioral factors, and precision treatment algorithms are needed. Full article

Heart failure (HF) remains a major cause of morbidity and mortality worldwide, with its prevalence continuing to rise due to an aging population and the increasing burden of cardiometabolic diseases. Advances in understanding HF pathophysiology—neurohormonal, inflammatory, and metabolic mechanisms—have led to significant improvements in diagnosis and management, emphasizing earlier detection and patient-centered approaches. Novel biomarkers have the potential to enhance risk assessment beyond traditional natriuretic peptides. Imaging advances can enhance structural and functional assessment, enabling more accurate phenotyping, disease characterization, and risk stratification. Recent advances and real-world data have been used to implement and optimize guideline-directed medical therapy (GDMT) for HF to reduce HF hospitalizations and cardiovascular mortality across the spectrum of HF etiologies. Adjunctive therapies are reserved for select patients with persistent symptoms or high-risk features despite optimal GDMT. Device- and transcatheter-based interventions include established and emerging technologies that address persistent symptoms, structural abnormalities, and hemodynamic abnormalities despite optimal GDMT, thereby expanding treatment options for high-risk patients. Collectively, these advancements highlight a paradigm shift toward precise, personalized approaches to HF management, thereby improving long-term outcomes across the spectrum of HF etiologies. Full article

Background: Postoperative bone healing can be impaired by systemic factors and surgical trauma, leading to delayed recovery. Photobiomodulation therapy (PBMT) has been proposed as a non-invasive method to enhance osteogenesis, but variability in protocols and outcomes limits its clinical use. Aim: To systematically review and synthesize evidence from randomized controlled trials (RCTs) evaluating PBMT’s effectiveness in promoting postoperative osteogenesis. Methods: A systematic search of PubMed, Embase, Scopus, and Cochrane Library was conducted following the PRISMA 2020 guidelines. Only RCTs comparing PBMT with sham treatment or standard care were included. Data on laser parameters, surgical indications, and outcomes such as bone regeneration, healing time, and implant stability were extracted. The risk of bias of the included randomized studies was evaluated using the Cochrane Risk of Bias 2 (RoB version 2) tool. Results: Twelve RCTs were included. PBMT consistently improved early soft tissue healing and reduced postoperative inflammation and edema. Some studies showed accelerated bone maturation, especially in grafted sockets and distraction osteogenesis, while others reported no significant long-term effects on implant stability or chronic lesion healing. Heterogeneity in laser parameters limited comparability. Conclusions: PBMT is a safe adjunct that reliably enhances early postoperative healing and may promote bone remodeling in selected cases. Standardized protocols and larger, high-quality RCTs are needed to confirm long-term benefits and optimize treatment parameters. Full article

(1) Context: Squamous cell carcinoma (SCC) is the most prevalent ocular neoplasm in horses, with a reported 45% recurrence rate when managed by surgery alone. (2) Objective: To evaluate the effect of adjunctive cisplatin biodegradable beads (CBBs) on recurrence rates of equine corneolimbal squamous cell carcinoma (SCC) and to document associated adverse effects. (3) Methods: Seventeen cases of histopathologically confirmed corneolimbal SCC in horses were retrospectively identified. Masses were surgically excised by keratectomy and/or conjunctivectomy under general anesthesia, followed by implantation of CBBs beneath conjunctival flaps at approximately 1 cm intervals around the excised area. Horses were monitored through owner follow-ups for up to five years postoperatively. (4) Results: Three horses (17.64%) experienced local mass recurrence within one year of treatment, and one horse (8.33%) relapsed approximately two years post-treatment. Minor local adverse effects—including chemosis (36%), hyperemia (64%), localized yellow discoloration (55%), and granular tissue formation (36%)—resolved within one to two months after surgery. Two horses developed bead-associated uveitis requiring closer ophthalmic monitoring. Vision was preserved in all but one relapsing case. (5) Conclusions: These findings suggest that adjunctive use of cisplatin biodegradable beads during surgical excision of equine corneolimbal SCC may significantly reduce recurrence rates and is generally well tolerated. Full article

Carpal tunnel syndrome (CTS) is the most common peripheral nerve entrapment disorder, with a lifetime prevalence estimated at approximately 10%. This narrative review explores the historical evolution, current management strategies, and emerging trends in CTS diagnosis and treatment. Early recognition of CTS led to the development of conservative interventions, including splinting, corticosteroid injections, and physical therapy, aimed at alleviating median nerve compression and associated symptoms. The advent of open carpal tunnel release established surgery as the definitive treatment for moderate-to-severe CTS, with subsequent refinements—such as mini-open and endoscopic techniques—focused on minimizing tissue trauma and expediting recovery. Comparative studies demonstrate similar long-term efficacy between surgical modalities, though endoscopic approaches often provide faster short-term recovery. Advances in diagnostic imaging, including high-resolution ultrasound, have improved early detection and dynamic assessment of median nerve compression. Emerging therapies, such as regenerative biologics, neuromobilization, and minimally invasive surgical innovations, offer promising adjuncts to current care. Despite substantial progress, further research is needed to clarify optimal patient selection, refine minimally invasive techniques, and explore regenerative interventions. This review underscores the importance of individualized, evidence-based, and patient-centered approaches to CTS management, integrating both established and emerging strategies to optimize functional outcomes and quality of life. Full article

Background: Hyperbaric oxygen therapy (HBOT) is considered a potential adjunctive modality to enhance tissue regeneration in oral and maxillofacial surgery. By increasing tissue oxygen availability, HBOT may support bone and soft-tissue repair under hypoxic and chronically inflamed conditions. Aim: This narrative review evaluates current experimental and clinical evidence regarding HBOT in high-risk dental indications, including osteoradionecrosis (ORN), medication-related osteonecrosis of the jaw (MRONJ), chronic osteomyelitis, poorly healing postoperative wounds, and procedures in patients with systemic comorbidities. Methods: A structured search of PubMed, Web of Science, and the Cochrane Library identified 123 relevant English-language publications (from 1 January 2000–September 2025) addressing HBOT mechanisms and clinical applications in oral and maxillofacial surgery, including clinical trials, observational studies, preclinical models, and systematic reviews. Results: Available evidence suggests that HBOT may improve healing outcomes and reduce complication rates in early-stage ORN and MRONJ when used as an adjunct to surgery and systemic therapy. However, findings in implantology—particularly in irradiated or diabetic patients—and in periodontal therapy remain limited, heterogeneous, and methodologically inconsistent. Conclusions: HBOT may be considered in selected clinical scenarios, particularly where healing is impaired by hypoxia or systemic disease. Nevertheless, current evidence remains insufficient to support routine use. Standardized, high-quality studies with clearly defined endpoints and uniform therapeutic protocols are needed to determine its clinical effectiveness and optimal indications. Full article

Background and Clinical Significance: Cutaneous Rosai-Dorfman disease (CRDD) is a rare, benign histiocytic proliferative disorder, accounting for approximately 3% of all Rosai-Dorfman disease (RDD) cases. Currently, the diagnosis of CRDD relies on invasive pathological examination due to the absence of reliable non-invasive alternatives. This case series evaluates the potential utility of high-frequency ultrasound (HFUS) as an adjunctive diagnostic tool for CRDD. Case Presentation: We present three CRDD cases, correlating HFUS features with histopathology. All cases showed hypoechoic lesions with varying infiltration depths and morphologies, though no specific diagnostic features were identified. HFUS clearly delineated involvement of the dermal and subcutaneous layers, assessed morphological characteristics like contour regularity and border definition, and evaluated vascularity. This information is crucial for clinical decision-making. HFUS also demonstrated value in therapeutic follow-up. In Case 1, it objectively showed a reduction in lesion size and decreased internal vascularity, providing clear evidence of treatment response. Conclusions: Although HFUS cannot independently diagnose CRDD and histopathology remains the gold standard, it serves as a valuable complementary tool. HFUS allows evaluation of deeper tissue structures, infiltration depth, and vascularity. As a non-invasive modality, it is useful for treatment monitoring, therapy guidance, and prognosis assessment. Integrating HFUS into the CRDD workflow enables more comprehensive and precise management. Full article