The University of Miami Leonard M. Miller School of Medicine (UMMSM) is the graduate medical school of the University of Miami. Founded in 1952, it is the oldest medical school in the state of Florida.
This review evaluates the role of intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents as peri-operative adjuvants in pars plana vitrectomy (PPV) for proliferative diabetic retinopathy (PDR). We synthesize current evidence on their use before, during, and after PPV, with emphasis on benefits, limitations, risks, and implications for surgical planning. Randomized trials and meta-analyses consistently show that preoperative anti-VEGF improves surgical safety by reducing intraoperative bleeding, shortening operative time, and lowering rates of early postvitrectomy vitreous hemorrhage, whereas long-term visual acuity benefits remain inconsistent. Intraoperative administration shows weaker and less consistent effects, and postoperative treatment is supported only by small studies, although it may reduce recurrent hemorrhage and anterior segment neovascularization in selected high-risk eyes. Bevacizumab remains the most studied and widely used agent. Newer anti-VEGF agents and higher-dose formulations may offer theoretical advantages, but comparative clinical data specifically in the setting of PDR vitrectomy remain limited. Preoperative anti-VEGF is currently the most evidence-based perioperative strategy, improving intraoperative conditions and early postoperative outcomes without clearly demonstrated durable functional gains. Critical gaps remain in optimal timing, agent selection, and real-world applicability, particularly in resource-limited settings. Large, pragmatic comparative trials and better risk-stratification tools are needed to refine perioperative anti-VEGF protocols in PDR surgery
Although most vestibular schwannomas (VS) occur sporadically, both sporadic and hereditary tumors share common molecular features beyond the loss of NF2. New evidence highlights the role of interconnected signaling pathways and epigenetic regulation in Schwann cell tumorigenesis, pointing toward potential molecularly targeted therapeutic strategies. This review synthesizes preclinical, molecular, and clinical evidence to examine genetic and epigenetic mechanisms underlying VS, therapeutic strategies, and contributors to hearing loss. A structured search of ClinicalTrials.gov identified 21 Phase 1–3 interventional therapeutic trials. VS pathogenesis is driven by NF2 loss and merlin deficiency, leading to dysregulation of Hippo/YAP-TAZ, PI3K/AKT/mTOR, VEGF, MAPK, and adhesion pathways. Epigenetic alterations, including DNA methylation, chromatin remodeling, non-coding RNAs, and SOX10 dysfunction, further shape tumor behavior. Clinical trial analysis revealed a predominance of early-phase, non-comparative studies, limited progression to later-phase trials, and incomplete results reporting, indicating gaps in high-quality evidence. Bevacizumab remains the most consistent systemic therapy for select NF2-related cases, while other agents such as icotinib, lapatinib, everolimus, selumetinib, and brigatinib have shown modest activity, primarily disease stabilization. Emerging approaches, including TEAD inhibition, PI3K/mTOR blockade, MEK inhibition, and combined signaling-epigenetic strategies, show preclinical promise. Hearing loss is multifactorial, involving tumor-secreted factors, inflammation, vascular changes, and inner ear damage alongside nerve compression. VS biology reflects integrated genetic and epigenomic dysregulation. Advancing care will require multi-omic classification, biomarker-driven trials, and combination therapies targeting both signaling and epigenetic vulnerabilities. Future management is expected to shift toward personalized, mechanism-based strategies aimed at durable tumor control while preserving hearing and quality of life.
This update and revision of the international guideline for urticaria was developed in accordance with the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. It is an initiative of the Global Allergy and Asthma Excellence Network (GA(2)LEN) and its Urticaria and Angioedema Centers of Reference and Excellence (UCAREs and ACAREs), with the participation of 210 delegates from 107 national and international societies, from 59 countries. The consensus conference was held on December 6th, 2024. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS). Urticaria is a frequent, mast cell-driven disease, defined by a rapid appearance of wheals, angioedema, or both. The lifetime prevalence of acute urticaria is estimated to be approximately 20%. Chronic urticaria, categorized as either chronic spontaneous urticaria or chronic inducible urticaria, is disabling, impairs quality of life, and affects performance at work and school, however, novel therapies are available. This updated version of the international guideline for urticaria covers the definition and classification of urticaria and outlines expert-guided and evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria.
ATN1-related neurodevelopmental disorder (ATN1-NDD) is a rare genetic condition typically diagnosed in infancy, characterized by profound developmental delay and hypotonia due to heterozygous pathogenic variants in the highly conserved HX motif of the ATN1 gene. We present a unique case of a 29-year-old male with mild intellectual delay, autism spectrum disorder, and microcephaly, diagnosed in adulthood through reclassification of a heterozygous in-frame tandem duplication variant (c.3188_3193dupTGCACC) within the HX motif. This case represents one of the mildest and latest diagnosed presentations of ATN1-NDD, expanding the known phenotypic spectrum. Notably, the patient’s genotype parallels the only other known mild case, suggesting a possible genotype-phenotype correlation distinct from the severe phenotypes typically observed. This report underscores the importance of genetic re-evaluation in adults with unexplained neurodevelopmental disorders and contributes valuable insight into the variability and natural history of ATN1-NDD.
