Clinical Approach Research Articles

Association between copper and Achilles tendon disease: a two-sample Mendelian randomization study

BackgroundThere is a clear association between micronutrients and Achilles tendon disease (AT). An increase in micronutrients may alleviate AT symptoms and have a therapeutic effect. The aim of this study is to clarify the causal relationship between 15 micronutrients (copper, zinc, magnesium, vitamins A, C, E, D, B6, B12, folic acid, carotene, iron, selenium, calcium, and potassium) and AT.MethodsWe employed the Mendelian randomization (MR) method to analyze the causal effects of micronutrients on the risk of AT. The SNPs related to micronutrients were obtained from a large-scale genome-wide association study (GWAS) of circulating micronutrients in European populations. Outcome data were obtained from a meta-analysis of AT in European-ancestry participants from the Finnish FINNGEN BIOBANK. The main analysis was conducted using the inverse variance weighting (IVW) method, with additional sensitivity and pleiotropy analyses performed.ResultsInverse variance weighting results indicated a causal relationship between copper and AT (P = 0.003, OR = 0.899, 95% CI = 0.839–0.964). Sensitivity analysis validated the robustness and reliability of this finding.ConclusionThis study revealed a causal relationship between copper and AT, with copper serving as a protective factor. This provides evidence of the causality between copper and AT, offering new insights for clinical research and therapeutic approaches in AT.

Clinical Presentations and Treatment Approaches in a Retrospective Analysis of 128 Intracranial Arteriovenous Malformation Cases

Background: Intracranial AVMs are a highly heterogeneous group of lesions that, while not very common, can pose significant risks. The therapeutic management of AVMs is complicated by ambiguous guidelines, particularly regarding which Spetzler–Martin grades should dictate specific treatment options. This study analyzed the clinical presentations and treatment approaches of 128 brain AVM cases managed between 2014 and 2022 at the National Institute of Neurology and Neurovascular Diseases in Bucharest, Romania. Methods: A retrospective analysis was conducted on patient demographics, clinical symptoms, Spetzler–Martin categorization, nidus localization, therapeutic management, and outcomes. Statistical analysis was performed using Python 3.10. Results: In our cohort of patients, the median age was 45 years, with a slight male predominance (67 males, 61 females). At admission, 51.5% presented with elevated blood pressure. The majority of patients had a Spetzler–Martin score of 2 (37.5%), followed by scores of 3 (31.3%) and 1 (20.3%). Treatment strategies included microsurgical resection in 32% of cases, conservative management in 31.2%, Gamma Knife radiosurgery in 22.6%, and endovascular embolization in 13.3%. Notably, open surgery was predominantly chosen for Grade II AVMs. The functional outcomes were favorable, with 69.5% achieving a good recovery score on the Glasgow Outcome Scale. Only four in-hospital deaths occurred, all in patients who underwent open surgery, and no deaths were recorded during the two-year follow-up. Conclusions: AVMs within the same Spetzler–Martin grade display considerable complexity, necessitating personalized treatment strategies. Our findings highlight the limitations of open surgery for Grade I cases but affirm its effectiveness for Grade II AVMs.

The effect of oral cavity condition on expression of saliva biomarkers in patients with oral mucosa pathology

Introduction. Despite visual accessibility of the elements of tumor lesions in the oral mucosa, patients with this pathology rarely seek medical help. Regeneration of the mucosa is a long process taking varying time depending on the location of the lesions. Asymptomatic tumor process leads to its diagnosis at late stages.Aim. To develop clinical and proteomic approach to diagnosis of malignancies of the oral mucosa at the stage of out-patient dentist appointment.Clinical observations. Examples of extended clinical, dental and immunoenzymatic monitoring in patients with elements of tumor lesions of the oral mucosa with long-term course are presented.Conclusion. The use of extended clinical, dental and immunoenzymatic analysis of oral fluid in patients with elements of tumor lesions of the oral mucosa allows to diagnose this pathology early.

Abstract 4132752: The immune checkpoint landscape in human atherosclerosis: influence of lipid lowering and type 2 diabetes

Immune checkpoint inhibitor (ICI) therapies substantially increase the risk of atherosclerotic cardiovascular events in cancer survivors. Here, we mapped the expression of immune checkpoints (ICs) within human atherosclerotic plaques, unraveling an intricate local network of immune cell-cell interactions in the context of relevant comorbidities like dyslipidemia and diabetes. Our findings identified a population of mature, regulatory CCR7 + FSCN1 + dendritic cells as pivotal orchestrators of IC-mediated signaling within human and murine plaques, a function akin to their role in tumor environments. In clinical cohorts, type 2 diabetes diminished CCR7 + FSCN1 + dendritic cells within atherosclerotic plaques and dampened interactions steered by PD-1 or CTLA4 consistently across immune cell subpopulations. This effect was also present and further decreased by lipid lowering in the circulation, where CD86–CTLA4 was among the most prominent IC pairs signaling between regulatory T cells and myeloid populations including CCR7 + FSCN1 + dendritic cells. These findings underline the vulnerability of atherosclerotic plaques to cancer immunotherapies and underscore the critical impact of cardiometabolic disease and lipid-lowering strategies on the atherosclerotic IC landscape, offering a framework toward the reshaping of clinical approaches.

Management of the Expected Difficult Airway with Planned One-Lung Ventilation: A Retrospective Analysis of 44 Cases

Abstract Background Difficult airway management is essential in anesthesia practice. Particular challenges are posed to patients who require intraoperative one-lung ventilation. Specific guidelines for these scenarios have been lacking. The recent update of German guidelines incorporates recommendations for securing the airway in anticipated difficult airway scenarios in patients requiring one-lung ventilation. However, scientific data on this specific topic is rare. Methods A retrospective analysis was conducted on adult patients undergoing thoracic surgery with one-lung ventilation from 2016 to 2021. During these years, the standard of practice has been in line with the now published guidelines. Patients with anticipated difficult airways were identified, and airway management strategies were analyzed. Results Among 3,197 anesthetic procedures, 44 cases involved anticipated difficult airways, primarily due to prior head and neck tumor treatment. Nasal bronchoscopic awake intubation followed by oral reintubation under videolaryngoscopic inspection and the use of bronchial blockers was the standard procedure. No severe complications were recorded, and one-lung ventilation was maintained successfully in all cases. Discussion The study highlights the challenges of managing difficult airways during thoracic surgery. Recommendations align with recent guidelines, emphasizing the importance of tailored approaches. The use of single-lumen tubes with bronchial blockers appears favorable over double-lumen tubes, offering comparable ventilation quality with reduced risks. Conclusion Despite limitations, the study underscores the safety and efficacy of tailored airway management strategies during one-lung ventilation in patients with anticipated difficult airways. The presented approach offers patient safety and practicability. Further multicenter studies are warranted to validate these findings and refine clinical approaches.

Abstract 4136032: Digital Biomarkers Associated With Coronary Artery Calcium And Traditional Risk Factors Extracted From Facial Photos Through Multi-Label Deep Learning For Detecting Coronary Artery Disease

Background: Biomarkers like coronary artery calcium (CAC) and traditional risk factors are well-validated for coronary artery disease (CAD) assessment but not always available, and with limited workup efficiency and potential radiation risk. Facial features contain biological information related to atherosclerosis. Aims: We aim to extract CAC and traditional risk factor-associated digital biomarkers from facial images and evaluate their value in predicting CAD status compared with conventional clinical approaches. Methods: Suspected individuals referred for confirmatory CAD evaluation across nine centers were included. Participants in one center constituted the derivation set. External validation included one dataset of participants from a different time period in the derivation center and the other dataset from the other eight centers. We developed a multi-label deep-learning model to extract digital biomarkers from facial photos based on a multi-dimensional label of CAC score and eight traditional risk factors to comprehensively represent coronary atherosclerosis risk profile. The extracted digital biomarkers were evaluated for both effectiveness in reflecting components of the multi-dimensional label and clinical value in predicting obstructive CAD. Results: A total of 13248 facial photos from 3312 eligible participants (mean age, 58.5 years; 517 [25.9%] female) were included. In external validation, a set of digital biomarkers (FacialCAD) were extracted, effectively reflecting components of the multi-dimensional label, especially for CAC stratification (CAC>0, AUC 0.919 [0.885 – 0.949]; CAC≥100, AUC 0.906 [0.876 – 0.933]) and nearly perfect prediction for the age and sex. The performance of the FacialCAD in predicting obstructive CAD (AUC 0.721 [0.694–0.748]) significantly outperformed two guideline-recommended CAD models (0.721 vs. 0.653, P<0.001; 0.721 vs. 0.686, P=0.032), with further significant improvement when combined with these models (△AUC= +0.085, P<0.001; △AUC= +0.068, P<0.001). Conclusion: FacialCAD, a set of CAC and risk factors-associated novel digital biomarkers extracted from facial images, exhibited superior and incremental value to conventional clinical approaches in predicting CAD status.

Holistic Intervention Strategies to Mitigate Premature Deliveries: Evidence-Based Community and Clinical Approaches

No abstract available

Integrating transcriptomic data and digital pathology for NRG-based prediction of prognosis and therapy response in gastric cancer

Background Cancer is characterized by its ability to resist cell death, and emerging evidence suggests a potential correlation between non-apoptotic regulated cell death (RCD), tumor progression, and therapy response. However, the prognostic significance of non-apoptotic RCD-related genes (NRGs) and their relationships with immune response in gastric cancer (GC) remain unclear. Methods In this study, RNA-seq gene expression and clinical information of GC patients were acquired from The Cancer Genome Atlas and the Gene Expression Omnibus databases. Cox and LASSO regression analyses were used to construct the NRG signature. Moreover, we developed a deep learning model based on ResNet50 to predict the NRG signature from digital pathology slides. The expression of signature hub genes was validated using real-time quantitative PCR and single-cell RNA sequencing data. Results We identified 13 NRGs as signature genes for predicting the prognosis of patients with GC. The high-risk group, characterized by higher NRG scores, demonstrated a shorter overall survival rate, increased immunosuppressive cell infiltration, and immune dysfunction. Moreover, associations were observed between the NRG signature and chemotherapeutic drug responsiveness, as well as immunotherapy effectiveness in GC patients. Furthermore, the deep learning model effectively stratified GC patients based on the NRG signature by leveraging morphological variances, showing promising results for the classification of GC patients. Validation experiments demonstrated that the expression level of SERPINE1 was significantly upregulated in GC, while the expression levels of GPX3 and APOD were significantly downregulated. Conclusion The NRG signature and its deep learning model have significant clinical implications, highlighting the importance of individualized treatment strategies based on GC subtyping. These findings provide valuable insights for guiding clinical decision-making and treatment approaches for GC.

Features and complexity of treatment of BRCA-associated ovarian cancer, chronic disease: literature review

We analyzed literature data on the peculiarities of the clinical manifestation and therapeutic approaches ofB RCA-associated ovarian carcinomas. The ESMO-ESGO consensus emphasised the importance of determining BRCA1/2 status in ovarian cancer patients for planning the entire treatment strategy. BRCA-associated carcinomas differ significantly from sporadic forms in terms of clinical course, response to systemic therapy, spectrum of drugs which are used for treatment, mechanisms of chemoresistance development, and prognosis. This category of patients needs new therapeutic approaches, including the development of tactics to overcome chemoresistance and modification of the entire combined treatment programme.

Bioactive Self‐Assembled Nanoregulator Enhances Hematoma Resolution and Inhibits Neuroinflammation in the Treatment of Intracerebral Hemorrhage

AbstractHematoma and secondary neuroinflammation continue to pose a significant challenge in the clinical treatment of intracerebral hemorrhage (ICH). This study describes a nanoregulator formed through the self‐assembly of Mg2+ and signal regulatory protein α (SIRPα) DNAzyme (SDz), aimed at enhancing hematoma resolution and inhibiting neuroinflammation in the treatment of ICH. The structure of SDz collapses in response to the acidic endo/lysosomal microenvironment of microglia, releasing Mg2+ and the SIRPα DNAzyme. The Mg2+ then acts as a cofactor to activate the SIRPα DNAzyme. By blocking the CD47‐SIRPα signaling pathway, microglia can rapidly and effectively phagocytose red blood cells (RBCs), thereby promoting the clearance of the hematoma. Simultaneously, Mg2+ reset the microglia to the M2 phenotype by inhibiting the MYD88/MAPK/NF‐κB signaling pathway, thereby modulating the inflammatory microenvironment of ICH. This co‐delivery and synergistic strategy resulted in a significant reduction in hematoma size, decreasing from 11.90 to 5.84 mm3, and promoted recovery from ICH with minimal systemic side effects. This simple yet highly effective nanoplatform, which involves complex synergistic mechanisms, proves to be effective for ICH therapy and holds great promise for introducing novel perspectives into clinical and translational approaches for ICH.

Actionable Variants of Unknown Significance in Inherited Arrhythmogenic Syndromes: A Further Step Forward in Genetic Diagnosis

Background/Objectives: Inherited arrhythmogenic syndromes comprise a heterogenic group of genetic entities that lead to malignant arrhythmias and sudden cardiac death. Genetic testing has become crucial to understand the disease etiology and allow for the early identification of relatives at risk; however, it requires an accurate interpretation of the data to achieve a clinically actionable outcome. This is particularly challenging for the large number of rare variants obtained by current high-throughput techniques, which are mostly classified as of unknown significance. Methods: In this work, we present a new algorithm for the genetic interpretation of the remaining rare variants in order to shed light on their potential clinical implications and reduce the burden of unknown significance. Results: Our study illustrates the potential utility of our individualized comprehensive stepwise analyses focused on the rare variants associated with IAS, which are currently classified as ambiguous, to further determine their trends towards pathogenicity or benign traits. Conclusions: We advocate for personalized disease-focused population frequency data and family segregation analyses for all rare variants that remain ambiguous to further clarify their role. The current ambiguity should not influence medical decisions, but a potential deleterious role would suggest a closer clinical follow-up and frequent genetic data review for a more personalized clinical approach.

Systematics of the Forms of Schizophrenia in the Concept of AV. Snezhnevsky

Background: Although there are international classifications of schizophrenia, the clinical approach to the systematization of schizophrenia developed by russian scientists has not lost its signifcance to date. The main role in the development of the schizophrenia of the national psychiatric school belongs to the famous Russian psychiatrist A.V. Snezhnevsky and his colleagues. The aim of review: to analyze the forms of the course of schizophrenia according to the concept of A.V. Snezhnevsky. Materials and methods: review of the main publications of A.V. Snezhnevsky and colleagues on the question of the doctrine of forms of schizophrenia course. Conclusion: The review summarizes the main research results of the national psychiatric school under the leadership of academician A.V. Snezhnevsky in the formation of the doctrine of schizophrenia.

A clinical approach for no prep direct composite veneers with opaquer/ tint to reshape a smile: a case report

Dental aesthetic has a profound influence on both self-esteem and social interactions. Patients desire changes in their smiles, while dentists aim for the preservation of dental and adjacent structures, as well as durability. In this context, no-prep resin veneers emerge as a potential solution, as they allow for the preservation of the maximum amount of healthy dental structure, pulp integrity, and dental strength. Nevertheless, treating darkened substrates poses a challenge, and conservative options like composite resins have gained recognition as restorative materials due to their aesthetic qualities and ability to preserve healthy dental tissue. A protocol can help dentists, especially by describing the stages of making direct no-prep veneers, achieving better clinical success. This article presents a clinical step-by-step guide approach to fabricating light-cured composite prepless veneers, using opaque and tints to mask dark backgrounds, and preserving the dental substrate in a patient with multiple restorations, changes in color, and shape. Light-cured composite prepless veneers comply with the principles of biomimetics and offer advantages such as conservation of dental structures, versatility, one-session preparation, cost, mechanical properties, and excellent aesthetics, however, skill with this technique is required.

Outcomes of patients with intermediate-risk neuroblastoma presenting with motor deficits relating to intraspinal tumor extension: A report from the Children's Oncology Group study ANBL0531.

Tumor invasion of the spinal canal is detected radiographically in approximately 15% of patients with newly diagnosed neuroblastoma (NB). The optimal clinical approach to maintain excellent survival outcomes while minimizing long-term sequelae is yet to be defined. Patients with intermediate-risk neuroblastoma (IR-NB) and radiographically identified intraspinal tumors who were treated on the Children's Oncology Group study ANBL0531 were studied prospectively to evaluate neurologic outcomes related to cord compression. Patients were defined as being symptomatic versus asymptomatic based on reporting of neurologic motor deficits at diagnosis. Patient characteristics, tumor biology, chemotherapy treatment, surgical interventions, and neurologic and disease outcomes are reported. Of the 92 patients with intraspinal tumors, 42 (46%) were symptomatic and most (73%) had complete resolution of symptoms. Age, degree of motor deficit, and duration of symptoms at diagnosis were not associated with complete resolution. While symptomatic patients were more likely to undergo upfront laminectomy, laminectomy was not associated with improvement of motor symptoms. Administration of additional chemotherapy beyond initial treatment assigned per protocol to achieve the treatment end point was not associated with achieving symptom resolution. Patients presenting with motor deficits due to intraspinal tumor had excellent survival and favorable neurologic outcomes, with the majority reporting complete resolution of motor symptoms regardless of severity and duration of symptoms at diagnosis or neurosurgical intervention. Prompt diagnosis and initiation of first-line chemotherapy treatment remain priority, while neurosurgical intervention should be reserved for patients with rapid neurologic deterioration. Biology-based therapy and tumor response should continue to be used to maintain favorable outcomes.

Ventricular arrhythmias in association with athletic cardiac remodelling.

Athletes are predisposed to atrial arrhythmias but the association between intense endurance exercise training, ventricular arrhythmias (VAs) and sudden cardiac death is less well established. Thus, it is unclear whether the 'athlete's heart' promotes specific arrhythmias or whether it represents a more general pro-arrhythmogenic phenotype. Whilst direct causality has not been established, it appears possible that repeated exposure to high-intensity endurance exercise in some athletes contributes to formation of pro-arrhythmic cardiac phenotypes that underlie VAs. Theories regarding potential mechanisms for exercise-induced VAs include repeated bouts of myocardial inflammation and stretch-induced cellular remodelling. Small animal models provide some insights, but larger animal and human data are sparse. The current clinical approach to VAs in athletes is to differentiate those with and without structural or electrical heart disease. However, if the athlete's heart involves a degree of pro-arrhythmogenic remodelling, then this may not be such a simple dichotomy. Questions are posed by athletes with VAs in combination with extreme remodelling. Some markers, such as scar on magnetic resonance imaging, may point toward a less benign phenotype but are also quite common in ostensibly healthy athletes. Other clinical and invasive electrophysiology features may be helpful in identifying the at-risk athlete. This review seeks to discuss the association between athletic training and VAs. We will discuss the potential mechanisms, clinical significance and approach to the management of athletes with VAs.

Trauma, Resilience, and Substance Use in Adolescents: A Review Article

Background: Adolescence is a sensitive phase of human life featuring changes in physical, emotional, and social characteristics. Many teens experience stressful events and trauma, which can affect their mental health and increase their risk of initiating and continuing substance use. Genetic vulnerabilities impact this relationship. In the face of trauma, while some adolescents are vulnerable, others navigate similar experiences differently, show resilience, and generally fare better without developing substance use problems. Understanding the multiple contributory factors that impact this relationship is critical in informing clinical approaches and program development. Objective: To describe the intricate dynamics between trauma, resilience, and substance abuse among adolescents. This review attempts to offer a synopsis that clarifies existing perspectives on trauma and substance use in adolescents while indicating areas for future research, clinical, and intervention programs in this critical area of adolescent well-being. Methods: A literature review was conducted to reveal available studies related to trauma, adolescent substance use, and resilience. Synthesis of findings from empirical studies, a detailed discussion on trauma and developmental factors while also addressing resilience elements alongside patterns of substance use is presented. Conclusion: Trauma, resilience, and substance use are linked in a tri-directional relationship, which is complex and dynamic. Adolescents with trauma are at higher risk of initiating and continuing substance. Resilience impacts treatment-seeking and engagement and may reduce relapse risk. Future research recommendations include improving the cultural sensitivity of interventions, studying the effects of marginalized identities, and ensuring rigorous evaluation of and progressive development of intervention programs. Results: The review highlights the bidirectional connections between trauma and substance use in adolescents. We include the consideration of resilience in adolescent responses to trauma. Resilience may reduce the risk of substance use, improve treatment-seeking and engagement in the treatment of SUD in adolescents, and reduce the risk of relapse, thereby suggesting it is a third dimension in the relationship between trauma and substance use. This review also provides evidence-based interventions and policies that are tailored to the specific needs of a diverse population of adolescents. We uncover the gaps in research, especially regarding cultural specifics and intersectionality among marginalized identities.

Mapping the Past Two Decades of Nutrition and Food Security in Iran: A Co-Word Network Analysis

Background: Food security in communities can prevent health complications, so investigators have made efforts to find its related factors through various fields. This study aims to draw a road map for nutrition and food security research in Iran. Methods: Web of Science, PubMed, Scopus, Embase, and Islamic World Citation Center were searched for eligible publications in nutrition and food security related to Iran for the two decades from 2001 to 2020. Content analysis was done by a co-word network technique using VOSviewer software. Results: Finally, 28,995 scientific publications among 50,444 search results were eligible to include in this study. The research map was drawn using 403,262 keywords obtained from the title and abstract of the papers. A 23.53% growth rate of publications was seen. Iranian articles were mainly published in scientific journals under 10 subject categories. The highly repeated keywords of "treatment", "plant", "age", "risk", and "consumption" were in publications. Moreover, the articles were categorized into thematic clusters of "environmental and climate change", "health ", "food industry and food safety", and "agriculture and water resources management" which were related to nutrition and food security. An increasing trend was observed in the number of publications during the past two decades in Iran. Conclusion: The relation of clinical nutrition, malnutrition, diet, and in recent years, food production and climate change with food security have been extensively studied by Iranian researchers. However, they have neglected studies on public health and policy in food and nutrition security, which reveals their dominant clinical or agricultural approach.

Evolving national guidelines for the treatment of children and adolescents with gender dysphoria: International perspectives

From the early years of this century, many Western countries adopted the “Dutch Protocol” as a new medical pathway for treating children and adolescents with childhood-onset gender dysphoria. On this approach, gonadotrophin-releasing hormone agonists (GnRHa) were used to suppress puberty, followed by cross-sex hormones (testosterone or oestrogen). This perspective article traces—in each of the countries where we, the authors, live and work—how the Dutch Protocol came to be incorporated into clinical practice or formally adopted into national guidelines. Over time, guidelines across different countries were progressively shaped by a rights-based approach that removed previous safeguards and increased availability of gender-reassignment medical interventions for children and adolescents. From 2010 onward, two developments raised new concerns, generating alternate perspectives and wide-ranging differences in clinical approach. Numerous countries reported an unexpected increase in adolescent-onset presentations, especially among girls. During the same period, an increasing number of individuals who had undergone gender-reassignment medical interventions as minors reported harm and regret. Worldwide, questions were raised about the safety of clinical guidelines for children and adolescents presenting with gender dysphoria. Government bodies in Finland, Sweden, the United Kingdom, and the U.S. state of Florida commissioned systematic reviews pertaining to hormone treatments and issued formal reports. In a parallel process, “conversion therapy” laws, passed in many countries, closed access to exploratory psychotherapy that enables exploration of gender-identity issues from a neutral therapeutic stance. Taken together, these three developments introduced evidence-based and legal considerations into the debate, resulting in tensions that remain unresolved.

Reflections on critical care ultrasound training: clinical analysis, protocol, view, approach and practice-workflow (CPVAP) modular training and base training model

Reflections on critical care ultrasound training: clinical analysis, protocol, view, approach and practice-workflow (CPVAP) modular training and base training model

Sodium-glucose cotransporter 2 inhibitors and glaucoma in patients with type 2 diabetes

Purpose: Pleiotropic cardiovascular benefits of sodium glucose co-transporter 2 inhibitors (SGLT2i) have been demonstrated in patients with type 2 diabetes mellitus due to vascular remodeling effects. It is unclear whether a similar benefit may be seen for glaucoma. The purpose of this study is to assess the effect of SGLT2i on the risk of glaucoma in patients with type 2 diabetes. DesignTarget trial emulation using a population-based, propensity score-matched clinical cohort approach. MethodsSetting: Population-based, propensity score-matched clinical cohort study. Study Population: Adults with type 2 diabetes in the United States who newly initiated treatment with SGLT2i, dipeptidyl peptidase 4 inhibitors (DPP4i), or glucagon-like peptide-1 receptor agonists (GLP1RA) between 2013 and 2023. After propensity score matching, 722,446 patients were included in the SGLT2i arm and the DPP4i arm, respectively. Participants were matched based on age at index, race and sex, comorbidities, and concomitant use of medications. ExposureTreatment with SGLT2i for type 2 diabetes. Main Outcome Measure(s)Incidence of new-onset glaucoma and its subtypes after initiation of SGLT2i, DPP4i, or GLP1RA. Subgroup analyses were performed to demonstrate the effect of individual SGLT2i on incident glaucoma. ResultsPatients on SGLT2i compared to those on DPP4 had a lower risk of glaucoma (HR: 0.815, 95% confidence interval [CI]: 0.794, 0.837), including open-angle glaucoma (HR: 0.755, 95%CI: 0.729, 0.781) and primary angle-closure glaucoma (HR: 0.592, 95%CI: 0.540, 0.650). Among all SGLT2i, ertugliflozin (HR: 0.668, 95%CI: 0.512, 0.871) was associated with the lowest risk of glaucoma, followed by empagliflozin (HR: 0.727, 95%CI: 0.696, 0.759), then dapagliflozin (HR: 0.814, 95%CI: 0.774, 0.855). The protective effect of SGLT2i on glaucoma was validated when compared with GLP1RA (HR: 0.932, 95%CI: 0.906, 0.959). Conclusions: Patients on SGLT2i, especially ertugliflozin and empagliflozin, had a significantly lower risk of incident glaucoma compared to those on DPP4i, an association that was less robust but significant in a sensitivity analysis using GLP1RA as the active comparator. SGLT2i had a protective effect for both open-angle glaucoma and angle-closure glaucoma.