Citations

Objective Glaucoma and cancer are debilitating diseases with increasing global prevalence and morbidity. However, current literature lacks a systematic consolidation of their relationships and interactions. This systematic review aims to (A) summarize the association between intraocular/non-ocular cancers and their treatments with the prevalence and etiology of glaucoma, (B) explore glaucoma as a risk factor for complications or poor prognosis for intraocular cancer, and (C) explore the management of glaucoma secondary to cancer therapies. Methods A systematic search was performed from inception to July 2025 across three databases with variants of ‘cancer’ and ‘glaucoma’ as search terms. Findings were narratively synthesized. Results Of 8,103 identified studies, 44 were included in this review. Eighteen studies reported increased glaucoma prevalence amongst intraocular and non-ocular cancer patients. Fifteen studies suggested increased risk of regional invasion, metastases, and high-risk histopathologies when intraocular cancers co-occurred with glaucoma. Corticosteroids in cancer therapy have been linked to intraocular pressure (IOP) elevation, while androgen deprivation therapy was associated with lowered glaucoma risk. Conclusion Given the relationship between glaucoma and intraocular/non-ocular cancers, strategies to monitor and manage glaucoma risk following cancer diagnosis and/or therapy may be considered. Glaucoma may be an early sign of complications in intraocular cancers.

This cross-sectional study examines sexual orientation-related discrimination among lesbian, gay, bisexual, and nonheterosexual (LGB+) medical students with disabilities.

Abstract Objective Pediatric epilepsy surgery is well established, but contemporary global data on referral and presurgical evaluation practices are lacking. This International League Against Epilepsy (ILAE) Pediatric Epilepsy Surgery Task Force study provides an updated overview of current trends and regional differences. Methods Group‐level data were collected from 61 epilepsy surgery programs (49 pediatric‐only) across 29 countries and six continents, identified through ILAE networks, and included all children and adolescents treated in 2023 who underwent presurgical evaluation/epilepsy surgery. Results Group‐level data were available for 2427 patients. Mean age at surgery was 9.1 ± 4.9 years; mean epilepsy duration was 5.3. At surgery, 3.2% were <1 year old (highest in Oceania: 5.1%), and 6.1% were nonpharmacoresistant (highest in Europe: 15.0%). Prior neurosurgery was reported in 14.2% (highest in North America: 28.8%), including 8.0% resections (6.1% for epilepsy, 1.5% for tumors; highest in Oceania: 16.5%), 2.3% disconnections (1.3% corpus callosotomy; highest in South America: 4.7%), and 4.2% neuromodulation (3.7% vagal nerve stimulation, .2% responsive neurostimulation, one deep brain stimulation; highest in North America: 12.2%). Developmental and epileptic encephalopathies (DEEs) at surgery included Lennox–Gastaut syndrome (7.4%), infantile epileptic spasms syndrome (5.1%), and DEE with spike–wave activation in sleep (1.5%). Presurgical investigations included fluorodeoxyglucose positron emission tomography (52.6%; highest in Oceania: 79.7%), genetic testing (46.8%; highest in Asia: 54.3%), magnetic resonance imaging (MRI) postprocessing (32.4%; highest in South America: 53.0%), functional MRI (fMRI; 15.2%; highest in North America: 40.3%), magnetoencephalography (11.9%; highest in North America: 39.3%), single photon emission computed tomography (9.6%; highest in North America: 22.2%), high‐density electroencephalography (EEG; 1.9%; highest in Europe: 4.7%), source localization (1.6%; highest in Oceania: 7.6%), Wada test (1.2%; highest in North America: 3.5%), and EEG‐fMRI (.5%; highest in Europe: 1.1%). Significance Despite some early surgeries, including in infancy and before pharmacoresistance, mean epilepsy duration before surgery remains >5 years. Reoperations are common, with resection more frequent than neuromodulation. Genetic testing in nearly half of patients reflects its growing relevance, and the high rate of DEEs underscores the complexity of surgical candidates.

Abstract Nonmyeloablative-related haploidentical allogeneic stem cell transplantation (NMAC-HID allo-HSCT) has emerged as an additional treatment to achieve durable remission in sickle cell disease (SCD), a prevalent blood disorder characterized by painful vaso-occlusive crises and chronic anemia. The standard of care (SOC) for SCD includes hydroxyurea, pain management, and blood transfusion, but patients with SCD still lose several decades of life expectancy. Gene therapy (GT) for SCD is the other treatment for lifelong disease amelioration in SCD, with accessibility limited by cost and manufacturing capacity in the United States and globally. Two recent prospective studies that evaluated NMAC-HID allo-HSCT validated haploidentical allotransplantation as an efficacious and accessible treatment option in the era of GT. Given the ongoing price negotiation across jurisdictions for GT implementation and the absence of cost-effectiveness data comparing NMAC-HID allo-HSCT and GT, we conducted a cost-effectiveness analysis of NMAC-HID allo-HSCT vs GT vs SOC for adults and children living with SCD. The primary outcomes were the incremental cost-effectiveness ratio and the net monetary benefits across these 3 strategies. The secondary outcome was the maximum cost-effective threshold price for GT compared with NMAC-HID allo-HSCT. Treatment with SOC, NMAC-HID allo-HSCT, and GT accrued 14.3, 20.1, and 22.1 quality-adjusted life-years at costs of $1.22 million, $1.15 million, and $2.75 million, respectively. NMAC-HID allo-HSCT was the cost-effective strategy compared with GT in 100% of 10 000 Monte Carlo iterations across the base case and all scenario analyses. The maximum cost-effective thresholds for GT vs SOC were $1.4 million in the United States and $4200 to $22 000 across India, Nigeria, and Tanzania, depending on willingness-to-pay thresholds.

As machine learning (ML)-based decision support tools proliferate in clinical practice, understanding how clinicians integrate personalized ML predictions alongside randomized controlled trial (RCT) evidence is critical. We designed a web-based clinical decision support system (CDSS) presenting survival and adverse event data from a simulated RCT and ML model across 12 synthetic multiple myeloma scenarios. In a within-subjects study with 32 physicians, we evaluated how clinicians synthesize competing evidence sources to make treatment decisions. When ML and RCT outputs were concordant, physicians reported greater confidence than with RCT data alone. When results were discordant, most physicians shifted toward the ML-supported treatment, often before reviewing any information about model training or validation, suggesting a tendency toward automation bias rather than algorithm avoidance. Despite reporting higher perceived reliability after viewing model quality disclosures, physicians were largely unable to describe the validation procedures they had reviewed. Taken together, these findings reveal that clinicians may over-rely on ML recommendations even when equipped with tools designed to support critical appraisal. We discuss implications for CDSS design, clinician training, and the institutional safeguards needed before ML-based systems are deployed in high-stakes oncology settings.

Among the transcriptional dependencies that sustain leukemic identity in acute myeloid leukemia (AML), the menin–KMT2A chromatin complex has emerged as a central regulatory node. The scaffold protein menin, encoded by MEN1, facilitates transcriptional activation of HOX and MEIS family genes during normal hematopoietic development. In AML, this physiologic and developmentally regulated role is co-opted to sustain constitutive HOX/MEIS-driven programs that block differentiation and maintain leukemic potential. Although dependency on menin is most clearly established in KMT2A-rearranged and NPM1-mutated AML, this vulnerability appears to arise from a shared transcriptional state characterized by persistent HOX activation rather than from any single genetic alteration. Pharmacologic disruption of the menin-KMT2A interaction collapses stemness-associated transcriptional networks, promotes myeloid differentiation, and attenuates leukemic self-renewal. Clinical activity observed with menin inhibitors provides translational validation of this dependency and establishes menin inhibition as a differentiation-based therapeutic strategy. In this review, we examine the molecular basis of menin-dependent transcriptional regulation in AML and its implications for therapeutic targeting with menin inhibitors and resistance to therapy.

ABSTRACT Objective Odontogenic sinusitis (ODS) ranges from isolated maxillary disease to pansinusitis. We compared patient characteristics, microbial and histopathological features, and symptom outcomes following endoscopic sinus surgery (ESS) between low and high radiographic burden ODS patients. Methods ODS patients undergoing ESS between 01/2013 and 08/2024 were reviewed. Preoperative CT scans were used to classify patients into high radiographic burden [with ostiomeatal complex (OMC) opacification] and low radiographic burden ODS [clear OMC]. Demographic, microbiological, and histopathological data were analyzed. Symptom improvement was assessed using pre‐ and post‐operative SNOT‐22 scores. Results Eighty‐seven patients were identified (high CT burden: 70; low CT burden: 17). High CT burden ODS was associated with older age ( p = 0.014), higher overall degree of inflammation ( p = 0.002), hyperplastic/papillary epithelial changes ( p = 0.034), and neutrophil infiltration ( p = 0.003). Culture of classic ODS bacteria ( Fusobacterium spp., Prevotella spp., mixed anaerobes, Streptococcus anginosus group) did not correlate with CT disease burden ( p = 0.110). No independent predictors of radiographic high‐burden disease were identified. Post‐ESS, significant reduction in total and rhinologic SNOT‐22 scores was only observed in the radiographic high‐burden ODS group ( n = 39; median reductions: 23 and 12 respectively; p < 0.001). Conclusion High radiographic burden was associated with older patients and with tissue inflammation level. Classic ODS bacterial profile did not associate with increased CT burden. While these findings remain exploratory, the observed differences in inflammatory and symptomatic profiles between groups suggest that radiographic burden warrants further study as a potential factor in ODS clinical decision‐making. Level of Evidence 3.

Ziftomenib - a potent, selective, oral menin inhibitor - is approved as monotherapy for adults with relapsed/refractory (R/R) NPM1-mutated acute myeloid leukemia (NPM1-m AML). The KOMET-007 phase 1 trial investigated clinical activity and tolerability of ziftomenib in combination with standard therapies for R/R and newly diagnosed AML. Here, we report outcomes of adults with R/R NPM1-m AML treated with ziftomenib plus venetoclax/azacitidine. In phase 1a, patients received ziftomenib 200, 400, or 600 mg once daily with standard doses of venetoclax/azacitidine. In phase 1b, ziftomenib 600 mg was selected for expansion. Sixty-seven patients were treated (27 phase 1a; 40 phase 1b). Median age was 66 years, and 55% were men. Median number of prior therapies was 1 (range 1-8); 55% received prior venetoclax and 22% had prior transplantation. Most common (≥20%) grade ≥3 treatment-emergent adverse events were leukopenia (34%), thrombocytopenia (28%), febrile neutropenia and neutropenia (25% each). Six patients developed QTc prolongation (1 ziftomenib-related; grade 1), and 2 experienced differentiation syndrome (grade 3); all events were successfully managed. In patients receiving ziftomenib 600 mg, composite complete remission (CRc) rate was 46% (22/48), with 67% (12/18) achieving central measurable residual disease (MRD) negativity (&lt;0.01% threshold). In venetoclax-naïve and -exposed patients, CRc rates were 70% (16/23) and 24% (6/25), with MRD-negativity rates of 75% (9/12) and 50% (3/6), respectively. Median duration of response was 8.6 months, and median overall survival was not reached. The combination of ziftomenib 600 mg with venetoclax/azacitidine was well tolerated with deep and durable clinical activity in R/R NPM1-m AML. This trial was registered at www.ClinicalTrials.gov as #NCT05735184.

Abstract Isolated cardiac sarcoidosis (iCS), defined by granulomatous inflammation limited to the myocardium, represents the most diagnostically challenging and prognostically adverse form of sarcoidosis. As it is fundamentally a diagnosis of exclusion, iCS diagnosis relies on the absence of extracardiac sarcoid and the integration of multimodality imaging, endomyocardial biopsy, and molecular testing, each with inherent limitations. Cardiac magnetic resonance and positron emission tomography provide complementary assessment of inflammation, fibrosis, and ventricular function, enhancing diagnostic confidence. Electroanatomic mapping-guided biopsy may improve histologic yield, whereas genetic testing helps exclude phenocopies such as arrhythmogenic, hypertrophic, or dilated cardiomyopathies. Circulating biomarkers remain non-specific but may complement imaging-based algorithms. Future research should focus on harmonized imaging protocols, non-FDG radiotracers, and molecular tissue profiling to refine activity assessment and guide therapy. Multimodal, probability-based frameworks represent the most promising approach for earlier, more accurate diagnosis and risk stratification in iCS.