Citations

Abstract Background Glioblastoma (GB) exhibits marked tumor microenvironmental heterogeneity, contributing to both therapy resistance and poor survival outcomes. Intercellular adhesion molecule 1 (ICAM1) is an inflammation-associated adhesion molecule implicated in immune-stromal interactions, but its clinical and biological significance in GB remains incompletely defined. Methods We performed ICAM1 immunohistochemistry, bulk RNA sequencing, DNA methylation analysis, single-nucleus RNA sequencing, and preoperative MRI-derived morphologic feature analysis across multi-institutional cohorts of treatment-naïve IDH-wildtype GB. Results High ICAM1 expression at both transcript and protein levels is associated with shorter overall survival, particularly within the mesenchymal transcriptional subtype. ICAM1 expression is inversely associated with promoter methylation. Single-nucleus RNA-sequencing analysis shows that ICAM1-high tumors are enriched for mesenchymal, hypoxia, stress-associated, and immunosuppressive myeloid programs, suggesting that ICAM1 reflects a multicompartment inflammatory tumor ecosystem. ICAM1 expression, tumor surface irregularity, and patient age are independently prognostic and minimally correlated, capturing complementary clinical, imaging, and molecular features of GB biology. When combined, our Clinical-Imaging-Molecular (CIM) framework refines outcome prediction across independent GB cohorts using routinely available clinical data, conventional imaging, and standard immunohistochemistry. Conclusions ICAM1 characterizes an immune-remodeled, stress-adapted GB ecosystem associated with poor clinical outcomes. Integrating patient age, surface irregularity, and ICAM1 expression yields a scalable and clinically accessible prognostic framework for GB, supporting tailored outcome prediction, particularly in low- and middle-resource settings without routine access to advanced molecular profiling.

Purpose: To describe the refractive results of cataract surgery in patients with high corneal astigmatism treated with implantation of custom-made toric intraocular lenses (IOLs). Methods: This retrospective cohort analysis of eyes implanted with high-cylinder (≥6.75 diopters [D]) custom-made toric IOLs was conducted at Rabin Medical Center, Petach Tikva, Israel. A control group of eyes implanted with standard toric IOLs (1.50 to 3.75 D) was also included. Postoperative IOL misalignment, uncorrected distance visual acuity (UDVA), residual refractive astigmatism (RA), and the prediction error (PE) of the toric IOL calculation using the Barrett Toric Calculator were assessed. Results: Twenty-two eyes of 22 patients were included. The mean ± standard deviation toric power was 9.67 ± 3.51 D (range: 6.75 to 19.00 D). Diagnoses included pellucid marginal degeneration (n = 7), keratoconus (n = 4), post-keratoplasty astigmatism (n = 3), and previous pterygium excision (n = 2). The mean postoperative UDVA was 0.28 ± 0.19 logarithm of the minimum angle of resolution (Snellen: 20/38). Mean absolute astigmatism decreased from 7.88 ± 3.15 D preoperatively (corneal) to 0.76 ± 0.87 D postoperatively (refractive) ( P < .001). One eye required redialing due to a 17° misalignment. Compared with the control group (41 eyes), the high-cylinder toric IOL group showed a slightly lower UDVA (20/30, P = .024) and a non-significant trend toward higher RA (0.58 ± 0.50, P = .930), as well as a significantly worse RA-PE, in both vector magnitude (1.47 vs. 0.62, P = .027) and vector dispersion (total bivariate variance 2.67 vs 0.40, px < 0.001 and py = 0.006). Conclusions: Customized high-cylinder toric IOLs significantly improve UDVA and reduce RA in eyes with extreme corneal astigmatism. Although slightly inferior to standard toric IOLs, they provide an effective treatment option for astigmatic correction in complex corneal pathologies with a central and relatively regular astigmatic component.

Objective: To evaluate access, clinical outcomes, engagement, and satisfaction associated with an advanced musculoskeletal virtual care model. Design: Retrospective cohort study of adults with musculoskeletal complaints referred to advanced orthopedic virtual physical therapy by Physical Medicine and Rehabilitation providers between July 2024 and April 2025. Outcomes included access to care, patient-reported outcome measures, pain intensity, plan-of-care completion, and patient satisfaction. Results: Of 137 referred patients, 86 (62.8%) completed evaluations; 70.9% of those (n=61) completed full care episodes — exceeding national completion benchmarks (71% vs. 43%). Among completers, 96% achieved Minimal Clinically Important Differences. Functional improvements were significant: Oswestry Disability Index −32.4, Neck Disability Index −29.5, Lower Extremity Functional Scale +26.6 (all P <.001). Pain decreased from 6.1 to 0.9 (−85%). Average care required 5.6 visits versus national benchmarks of 6–10. Patient satisfaction was exceptional (Net Promoter Score=100). Conclusion: Among patients who completed a full episode of care, this advanced virtual musculoskeletal model was associated with substantial functional improvement, pain reduction, and high satisfaction while requiring fewer visits than national averages. Because outcome analyses were limited to completers, these findings may not represent all referred patients. Prospective controlled studies are needed to evaluate effectiveness and scalability.

BACKGROUND AND OBJECTIVES: Access to the orbit, cavernous sinus, Meckel cave (MC), and infratemporal fossa (ITF) remains challenging due to the complex 3-dimensional anatomy and proximity to critical neurovascular structures. An extradural endoscopic orbitozygomatic (OZ) approach has the potential to provide a direct surgical corridor across these compartments while minimizing the limitations of compartment-specific corridors. METHODS: Five formalin-fixed, silicone-injected cadaveric heads (10 sides) were dissected using an extradural OZ approach under operative microscopy supplemented with 0° and 30° rigid endoscopes. After a two-piece OZ craniotomy, extradural dissection was performed toward the superior orbital fissure and foramen rotundum/ovale, combined with anterior petrosectomy and opening of MC. Anatomic exposure, corridor continuity, and visualization of key neurovascular structures were qualitatively assessed. RESULTS: The extradural endoscopic OZ approach created a direct working corridor from the lateral orbit to the ITF and petroclival region. Endoscopic augmentation enhanced visualization of the lateral cavernous sinus wall, trigeminal divisions (V 1 -V 3 ), cavernous internal carotid artery, medial orbital apex, deep infratemporal recesses, and the petroclival region. Anterior petrosectomy extended exposure toward the upper clivus and ventrolateral brainstem. Limitations included restricted microscopic visualization of the medial orbit and inferior ITF, which were partially mitigated by angled endoscopy. CONCLUSION: This cadaveric study demonstrates that the extradural OZ–anterior petrosectomy approach establishes a continuous anatomic corridor integrating the orbit, cavernous sinus/MC, ITF, and petroclival region, while defining its boundaries, areas of optimal exposure, and inherent limitations. As a qualitative study, the findings are descriptive in nature and do not include quantitative morphometric analysis.

Background: Fecal immunochemical tests (FITs), fecal occult blood tests (FOBTs), and multitarget stool DNA (mt-sDNA) tests are convenient, noninvasive colorectal cancer (CRC) screening strategies. However, delays in or failure to complete follow-up colonoscopy (FU-CY) after a positive noninvasive test are associated with higher CRC incidence, complications, and mortality. We sought to evaluate FU-CY rates, time to colonoscopy, and compliance predictors. Patients and Methods: This retrospective cohort study linked 2 data sources: Komodo Health Data with Exact Sciences Laboratories. Data were collected from January 2016 to June 2023 and analyzed in 2024. Study participants (ages 45–75 years) were individuals with positive stool-based CRC screening tests (FIT, guaiac-based FOBT, or mt-sDNA tests). FU-CY compliance was assessed at 30-day intervals up to 365 days, and logistic regression was used to identify predictors of FU-CY. Results: Among 362,646 participants, colonoscopy compliance was 77.1% for mt-sDNA and 45.1% for FIT/FOBT ( P <.001). Overall FU-CY compliance was lowest among Asian and Black populations, but was significantly higher in these subgroups for mt-sDNA versus FIT (Asian: 74.2% vs 41.1%; Black: 71.3% vs 44.6%). The strongest predictor of compliance was use of mt-sDNA (odds ratio, 3.98; P <.001). More than half of participants across all race groups who completed FU-CY after mt-sDNA did so within the first 120 days, whereas none of the FIT/FOBT racial subgroups reached 50% completion within 365 days. Conclusions: Timely completion of colonoscopy after a noninvasive test is critical, as failure to undergo colonoscopy or delays in completion are associated with increased CRC incidence and more advanced-stage disease. These findings demonstrate that mt-sDNA use may help close CRC screening disparity gaps compared with FIT testing. FU-CY adherence is higher, and time to colonoscopy is shorter following a positive mt-sDNA test versus FIT across all racial and ethnic subgroups.

The Philadelphia chromosome-negative myeloproliferative neoplasms (MPN) are a group of heterogenous hematologic malignancies characterized by the proliferation of blood cells and consist of myelofibrosis, polycythemia vera, and essential thrombocythemia. The NCCN Guidelines for MPN were developed as a result of meetings convened by a multidisciplinary panel with expertise in MPN, with the aim of providing recommendations for the comprehensive care of adults with these diseases. The panel of experts convenes at least once a year to discuss requested changes to the Guidelines and to evaluate emerging data. These Guideline Insights focus on some of the recent updates for myelofibrosis.