Myelodysplastic syndromes/neoplasms (MDS) comprise a heterogeneous group of clonal myeloid malignancies characterized by ineffective hematopoiesis and a variably increased risk of progression to acute myeloid leukemia (AML). Higher-risk MDS, as defined by the revised- and molecular International Prognostic Scoring System, remains largely incurable except through allogeneic hematopoietic stem cell transplantation. Management continues to rely primarily on hypomethylating agents, which were approved nearly two decades ago and remain the cornerstone of therapy despite their modest efficacy. Advances in molecular profiling and next-generation sequencing have greatly improved disease classification and prognostication tools. However, with the exception of IDH1 inhibitor ivosidenib, targeted therapies in higher-risk MDS remain the exception to the rule. Although numerous early-phase clinical trials have yielded promising signals, phase III trials have repeatedly failed to replicate these findings. This largely reflects the intrinsic biological complexity and heterogeneity of MDS, as well as logistical challenges in trial design and execution. Examining the history and evolution of investigational pharmacotherapy in higher-risk MDS may help identify where efforts to translate early phase successes into successful phase III trials have faltered. The expanding biological knowledge base and the design of better therapies will hopefully pave the way for future therapeutic breakthroughs.

ABSTRACT Introduction Ketamine has shown promise as a novel treatment for psychiatric disorders. This narrative expert review provides an update on recent advances in ketamine research. Areas covered Herein, we narratively summarize (1) new efficacy data from clinical trials, (2) real-world effectiveness data, (3) growing safety data, (4) alternative routes of administration, (5) optimization of treatment protocols, (6) considerations for enantiomer variants, and (7) new potential indications. Lastly, limitations and challenges to the progression of the field will be discussed. Expert opinion Evidence supporting the use of intravenous ketamine and intranasal esketamine for depression has dramatically increased with a large number of clinical trials and real-world effectiveness studies supporting antidepressant effects. Larger studies have provided reassuring data supporting an adequate safety profile, including safety data with long-term treatment. Alternative routes of administration have shown promise for improving scalability; however, efficacy as compared to intravenous ketamine remains unclear. Promising preliminary data support ketamine’s efficacy in other conditions, such as bipolar disorders, personality disorders, posttraumatic stress, and obsessive-compulsive disorder. Further research is needed to optimize protocols, such as combining ketamine with other interventions. Functional unblinding, expectancy-related bias, and treatment costs remain challenges for the field.

ABSTRACT Introduction Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic, heterogeneous inflammatory disorder of the sinonasal mucosa that substantially impairs quality of life. It is characterized by T2 or non-T2 inflammatory endotypes and often coexists with asthma or aspirin-exacerbated respiratory disease, complicating management due to high recurrence rates and limited disease-modifying options. Areas covered This review evaluates emerging pharmacotherapies for CRSwNP, emphasizing targeted biologics developed from mechanistic understanding of inflammatory pathways. Approved monoclonal antibodies, dupilumab, omalizumab, and mepolizumab, are discussed regarding their effects on nasal polyp size, symptom relief, and patient-reported outcomes, with reference to comparative efficacy and safety. Evidence is drawn from RCTs, meta-analyses, and real-world studies, highlighting both clinical benefits and current limitations. Emerging therapies targeting upstream epithelial cytokines (TSLP, IL-33) and complementary strategies, including small-molecule inhibitors, microbiome modulation, and advanced topical delivery systems, are also addressed. Expert opinion Biologics have transformed CRSwNP treatment, but challenges remain in cost, treatment duration, and patient selection. Integrating endotype characterization, biomarkers, and comparative effectiveness data is crucial for personalized management. Future advances are expected from upstream immune modulation, restoration of epithelial barrier integrity, and optimized local drug delivery, enabling mechanism-based, adaptive approaches that maximize efficacy while minimizing systemic exposure.

ABSTRACT Introduction Pediatric HIV remains a major global health challenge, with 1.4 million children living with HIV and persistent gaps in diagnosis, treatment coverage, and viral suppression. Despite increasing alignment between pediatric and adult guidelines toward rapid antiretroviral therapy (ART) initiation and integrase inhibitor (INSTI)-based regimens, many children remain unsuppressed and at risk of disease progression and drug resistance. Areas covered This review summarizes current evidence on when to start ART, how to select and optimize regimens, and the evolving burden of antiretroviral resistance in children and adolescents. It also examines major comorbidities (including malnutrition, metabolic complications, bone disease, and neurocognitive impairment) and their interaction with lifelong ART. Practical aspects of care are discussed, including baseline assessment, virological and immunological monitoring, and strategies to support adherence and retention. Finally, we outline emerging and pipeline agents and their potential role in the future management of pediatric HIV. Expert opinion Achieving durable viral suppression in children and adolescents requires earlier diagnosis, optimized child-friendly regimens, routine resistance testing, and integrated management of comorbidities. Key priorities include pediatric evaluation of long-acting and novel agents, development of improved immunologic and virologic markers, and scalable approaches to strengthen engagement in care and reduce global inequities.

ABSTRACT Introduction Dry eye disease (DED) is a chronic condition that can markedly impair visual function and quality of life. While tear substitutes remain the conventional first-line therapy, expanding knowledge of DED has opened the door to treatments designed to act on distinct pathogenic mechanisms. Areas covered An extensive literature review using PubMed, Scopus, and Web of Science was conducted to evaluate both established and emerging therapies for DED. This review encompasses conventional tear substitutes and their properties, immune-modulating agents, blood derived products and other biological agents, tear-conservation approaches, device-based interventions, and recently approved as well as investigational treatment options. Expert opinion The evolving understanding of DED supports a shift toward mechanism-based, personalized management that addresses inflammation, tear film instability, neurosensory dysfunction, and glandular insufficiency. Integrating targeted therapies, device-based interventions, and regenerative approaches with improved diagnostics may enable more predictable, proactive care. Rigorous research is still needed to optimize treatment selection and sequencing.

ABSTRACT Introduction Major depressive disorder (MDD) remains a leading global cause of disability, with substantial clinical and societal burden. Despite the wide availability of antidepressants, many patients experience inadequate response, partial remission, or treatment-resistant depression. Emerging pharmacological options beyond traditional monoaminergic agents have shown promise in phase 3 clinical trials, yet their integration into treatment algorithms remains limited. Areas covered This review summarizes current challenges in antidepressant therapy and examines phase 3 clinical evidence for newer agents across diverse depressive conditions, including postpartum depression, acute suicidal ideation, and treatment-resistant MDD. Data on efficacy, safety, and relapse prevention from pivotal trials of brexanolone, intranasal esketamine, dextromethorphan – bupropion, vortioxetine, and metabolism-based interventions such as glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are discussed. The positioning of these treatments within international clinical guidelines is also examined, highlighting inconsistencies and the lack of formal recommendations. A literature search was conducted in PubMed, Embase, Scopus, and ClinicalTrials.gov from January 2000 to June 2025. Expert opinion Newer antidepressants represent a shift beyond conventional approaches, offering rapid symptom relief and potential cognitive or metabolic benefits. However, limited guideline integration, insufficient long-term data, and implementation barriers restrict their clinical uptake. Clearer sequencing strategies and harmonized recommendations are needed to support more individualized depression management.