Abstract Objectives To compare the efficacy and safety of pharmacologic therapies for spontaneous epistaxis in hereditary hemorrhagic telangiectasia (HHT). Data Sources PubMed, Scopus, Embase, Web of Science, and the Cochrane Library were systematically searched up to August 2025. Review Methods Eligible randomized controlled trials evaluating bevacizumab, doxycycline, tranexamic acid, or β‐blockers versus placebo or standard care were included. Outcomes included epistaxis frequency and duration, hemoglobin (Hb), epistaxis severity score (ESS), transfusion or emergent‐care requirements, quality of life (QOL), and adverse events. Results Tranexamic acid did not significantly reduce epistaxis duration or frequency or improve Hb, and it did not change transfusion or emergent‐care needs, but it increased diarrhea (odds ratio 3.8, 95% confidence interval [CI] [1.7; 8.5]). Bevacizumab produced a modest reduction in epistaxis frequency (standardized mean difference −0.25, 95% CI [−0.47; −0.02]), without significant effects on duration, ESS, Hb, or QOL. Doxycycline showed no significant benefit for duration or frequency. Topical or systemic β‐blockers did not significantly affect ESS, QOL, Hb, or overall adverse events. Across agents, between‐study heterogeneity was generally low to moderate and CIs were wide, reflecting limited sample sizes. Conclusion No pharmacologic agent demonstrated consistent, clinically robust superiority over placebo across primary endpoints. Bevacizumab may modestly reduce bleeding burden, whereas tranexamic acid increases gastrointestinal toxicity without clear efficacy. Pharmacologic control of HHT‐related epistaxis remains suboptimal, underscoring the need for adequately powered trials with standardized outcome measures and optimized dosing and delivery strategies.
Electrochemical immunosensor-enabled liquid biopsy of extracellular vesicles for diagnosis of metabolic dysfunction-associated steatohepatitis
Abstract Accurate, noninvasive biomarkers for diagnosis and longitudinal monitoring of metabolic dysfunction–associated steatohepatitis (MASH) remain an urgent unmet clinical need. Here, we describe an electrochemical immunoassay that involves capturing hepatic extracellular vesicles (EVs) on antibody-modified electrodes followed by detecting EV-borne biomarkers using redox active gold nanoparticles (AuNPs). The intensity of electrochemical redox signal represents a quantitative measure of biomarker abundance. Three MASH-associated biomarkers—S100A11, TNF-α, and TGF-β1—were analyzed on hepatic EVs to assess steatotic, inflammatory, and fibrotic states of the diseased liver. The electrochemical signals for individual biomarkers were added into a composite EV MASH score. Plasma samples from 28 patients with MASH, 22 healthy controls, and 27 patients with non-MASH liver disease were scored in this manner, revealing 100% accuracy in the training cohort and >90% accuracy in an independent validation cohort. Our electrochemical immunosensor represents a minimally invasive liquid liver biopsy, offering a promising alternative to solid liver biopsies for screening and monitoring of MASH. One Sentence Summary Circulating hepatic extracellular vesicles carry biomarkers of liver injury enabling accurate, minimally invasive MASH diagnosis in blood.
Age-Specific Efficacy of Platelet-Rich Plasma in Tonsillectomy: A Systematic Review and Meta-Analysis
Background/Objectives: The objective of this study was to evaluate age-specific effects of intraoperative platelet-rich plasma (PRP) administration on postoperative pain, wound healing, and bleeding after tonsillectomy. Methods: PubMed, Embase, Scopus, Google Scholar, and Cochrane databases were searched from inception to October 2025. Randomized controlled trials comparing intraoperative PRP with placebo or no treatment in patients undergoing tonsillectomy were included. Data on postoperative pain, wound healing, and bleeding were extracted and analyzed using standardized mean differences (SMDs) and odds ratios (ORs) with 95% confidence intervals (CIs). Subgroup analyses were performed by age (adults versus children) and by postoperative day. Results: Nine randomized controlled trials comprising 442 participants were included. In adults, PRP significantly reduced postoperative pain (SMD = −1.26 [−1.70 to −0.81]) and improved wound healing (SMD = −1.43 [−2.65 to −0.22]). The analgesic effect was greatest during the early recovery period (postoperative days 0–5) and diminished thereafter. There were no significant differences in primary postoperative bleeding (OR = 0.49 [0.04 to 5.61]) or secondary postoperative bleeding (OR = 0.23 [0.02 to 2.16]) between the PRP and control groups. In children, PRP did not significantly affect pain or bleeding outcomes. Conclusions: Intraoperative PRP may reduce early postoperative pain and may promote mucosal recovery in adults. However, its clinical efficacy in children remains unclear. Further well-designed, age-stratified trials are warranted to clarify the role of PRP in enhancing postoperative recovery.
Effect of Exhalation Delivery System With Fluticasone for Chronic Rhinosinusitis: A Systematic Review and Meta-Analysis
An exhalation delivery system for fluticasone (EDS-FLU) is designed to deposit drug into sinonasal regions above the inferior turbinate, particularly sinus drainage pathways not reached by standard nasal steroid sprays. We evaluated the efficacy and safety of EDS-FLU for chronic rhinosinusitis (CRS). We reviewed four independent randomized controlled trials derived from three published articles identified through searches of PubMed, Embase, SCOPUS, Google Scholar, Web of Science, and the Cochrane Library up to April 2024. Outcomes included 22-item Sinonasal Outcome Test (SNOT-22) scores, nasal symptom scores, nasal polyp scores, patient global impression of change (PGIC), responder and surgical indication rates, and adverse events. Compared with EDS-placebo, EDS-FLU produced greater reductions in nasal polyp scores and SNOT-22 scores over 6 months. At 3 months, nasal congestion, facial pain, rhinorrhea, and olfactory dysfunction improved more with EDS-FLU, and PGIC responder and complete response rates were higher at 3 and 6 months. EDS-FLU reduced surgical indication and increased overall responder rates at 3 months but not at 6 months. Epistaxis and nasal septal erosion or ulceration occurred more frequently with EDS-FLU, whereas rates of headache, nasal congestion, nasopharyngitis, and upper respiratory infection were similar between groups. EDS-FLU provides clinically meaningful improvements in subjective and objective outcomes in CRS but is associated with an increased risk of local nasal adverse events, warranting individualized risk-benefit assessment.
Efficacy of a Combination Therapy of Montelukast and Antihistamines in Allergic Rhinitis: A Systematic Review and Network Meta-Analysis
ABSTRACT Objectives Xylitol, a low‐permeability sugar alcohol, is recommended for treating chronic rhinosinusitis (CRS) due to its ability to decrease liquid salt concentration at the airway surface. This study investigated the efficacy of xylitol nasal irrigation for the management of CRS and its postoperative care. Methods We analysed 7 studies with 263 participants after reviewing the studies that were retrieved from PubMed, SCOPUS, Embase, Web of Science, and Cochrane databases up to December 2024. Those comparing changes in endoscopic score, Sinonasal Outcome Test (SNOT), Nasal Obstruction Symptom Evaluation (NOSE), olfactory dysfunction, and CRS‐related visual analogue scale from baseline to post‐treatment between xylitol and normal saline nasal irrigation groups were analysed. Results Nasal irrigation with xylitol significantly improved sinonasal well‐being in CRS patients compared to irrigation with saline (SMD 0.6253, 95% CI [0.0067; 1.2438]; I 2 = 0.0%). Patients who underwent endoscopic sinus surgery showed substantial SNOT improvement (SMD 3.1284, 95% CI [0.5229; 5.7338]; I 2 = 86.1%), while no significant changes were observed in non‐ESS patients (SMD 0.2571, 95% CI [−0.4872; 1.0014]). The xylitol group also showed significant improvements in NOSE (SMD 0.5976, 95% CI [0.2297; 0.9656]; I 2 = 49.3%) and SNOT scores (SMD 0.3608, 95% CI [0.0724; 0.6493]; I 2 = 49.1%). However, there were no significant changes in endoscopic scoring (SMD 0.1309, 95% CI [−0.1777; 0.4396]; I 2 = 0.0%), olfaction (SMD −0.0292, 95% CI [−0.3633; 0.3050]; I 2 = 0.0%), or saccharine clearance time (SMD 0.3816, 95% CI [−0.3816; 1.1449]; I 2 = 61.6%). Xylitol irrigation was well tolerated, with minimal, transient side effects and no significant adverse events. Conclusion Nasal irrigation with xylitol significantly improves the subjective management of CRS and postoperative care compared to saline irrigation but does not alter objective outcomes.
Efficacy of Montelukast–Antihistamine Combination Therapy Versus Antihistamine Monotherapy in Allergic Rhinitis: A Systematic Review and Meta-Analysis
Objectives. Allergic rhinitis (AR) can substantially compromise daily functioning and well-being, and many patients require more than a single agent to obtain satisfactory symptom control. This study examined whether adding montelukast to antihistamine could manage AR symptoms and quality-of-life outcomes effectively.Methods. A review was performed in PubMed, Embase, Medline, Scopus, the Cochrane Library, and Google Scholar to identify eligible studies reported through April 2025. Eligible studies compared combination therapy with montelukast plus antihistamine against antihistamine monotherapy and reported nasal symptoms or rhinoconjunctivitis quality of life questionnaire (RQLQ) scores. Treatment effects were further examined by antihistamine class.Results. Fifteen studies including 2,882 subjects were analyzed. Combination therapy significantly improved daytime nasal symptoms (standardized mean difference [SMD] [95% CI], 0.44 [0.21–0.67]), nighttime nasal symptoms (0.12 [0.01–0.23]), and RQLQ scores (0.14 [0.00–0.27]) versus monotherapy. Individual nasal or ocular symptoms, sneezing, nasal obstruction, and rhinorrhea improved significantly, while nasal itching and ocular symptoms did not. Combinations with desloratadine and levocetirizine showed greater benefits than those with loratadine or fexofenadine.Conclusion. Montelukast–antihistamine combination therapy reduced overall symptoms and improved quality of life versus antihistamine monotherapy. The magnitude of benefit appears to vary depending on the specific antihistamine used, highlighting the possible value of individualized treatment strategies in the treatments of AR.
Efficacy of the Exhalation Delivery System With Fluticasone for Chronic Rhinosinusitis: A Systematic Review and Meta-Analysis
Objectives: Novel biomechanics of the exhalation delivery system can deliver fluticasone (EDS-FLU; XHANCE) to sinonasal areas above the inferior turbinate, especially sinus drainage pathways not reached by standard nasal sprays. This study aimed to evaluate the effectiveness of EDS-FLU in treating chronic rhinosinusitis (CRS). Methods: Studies were retrieved from PubMed, SCOPUS, Embase, Web of Science, and Cochrane databases up to April 2024. We analyzed 5 studies that compared EDS-FLU with a control group (exhalation delivery system with placebo) on various outcomes, including the 22-item Sinonasal Outcome Test (SNOT-22), nasal symptom scores (congestion, facial pain, olfactory dysfunction, and rhinorrhea), nasal polyp scores, surgical indication rate, and the incidence of adverse effects. Results: Five studies with 2129 patients were included. EDS-FLU significantly improved SNOT-22 score (−20.9657 [−23.5639; −18.3674]) and the polyp score (−1.5099 [−1.7810; −1.2388]) after 6 months. The incidence of epistaxis was significantly higher in the treatment group compared to the control group (OR = 5.7954 [2.1004; 15.9909]). Effects of EDS-FLU on polyp score (−0.6497 [−0.8186; −0.4807]), responder rate (OR = 2.1755 [1.2784; 3.7020]), complete responder rate (OR = 2.0423 [1.0109; 4.1262]), surgical indication rate (OR = 0.7313 [0.5459; 0.9797]), and SNOT-22 score (−6.1513 [−11.3054; −0.9972]) were significantly higher in the treatment group than in the control group. Conclusions: This study demonstrated that EDS-FLU (372 µg twice daily) produced statistically significant improvements compared to EDS-placebo in multiple subjective and objective outcomes, although some adverse effects, such as epistaxis, may occur.
Short‐Term Efficacy of Biologics in Recalcitrant Allergic Fungal Rhinosinusitis: A Systematic Review and Meta‐analysis
Abstract Objective Allergic fungal rhinosinusitis (AFRS) is characterized by type I immunoglobulin E (IgE)‐mediated hypersensitivity reactions to fungal antigens. This systematic review and meta‐analysis assessed the efficacy of biologics in the management of refractory AFRS. Data Sources PubMed, SCOPUS, Embase, Web of Science, and Cochrane. Review Methods Changes in Sino‐Nasal Outcome Test (SNOT)‐22 scores, endoscopic findings, serum eosinophil count, and total IgE levels were assessed in patients with refractory AFRS after receiving biologic therapy. Subgroup analyses were conducted to evaluate the individual efficacy of each biologic agent, including dupilumab, mepolizumab, and omalizumab. Results A total of 60 patients from 6 studies were analyzed. Biologics showed a significant improvement in SNOT‐22 scores (standard mean difference 1.1607 [95% CI 0.5549; 1.7664]), endoscopic scores (2.1953 [1.4181; 2.9725]), serum eosinophil count (1.1649 [0.7735; 1.5563]), and total IgE level (1.0700 [0.4052; 1.7348]). Dupilumab, mepolizumab, and omalizumab all enhanced SNOT‐22 and endoscopic scores. Additionally, dupilumab significantly reduced total IgE levels (1.2981 [0.4063; 2.1900]), whereas both dupilumab (0.9274 [0.1592; 1.6957]) and mepolizumab (1.2324 [0.9215; 1.5433]) significantly lowered the serum eosinophil counts. Conclusion The agents significantly improved nasal symptoms, laboratory findings, and endoscopic scores. These findings support the potential role of biologics as a therapeutic option for patients with AFRS who are unresponsive to conventional treatments.
Microencapsulation of pluripotent stem cell-derived pancreatic and liver cells: biological needs and technological solutions
This review describes approaches for encapsulation of pluripotent stem cells, the biomaterials used, strategies for differentiation into hepatocytes and β cells, and the impact of microencapsulation on cellular therapy.