Citations

Abstract Glioblastoma (GBM) is a highly aggressive brain tumor with poor survival outcomes and limited tools for accurate prediction of individual patient prognosis. While many prognostic models rely on advanced molecular testing, such methods are not routinely accessible across most clinical settings. In this study, we identify a practical and clinically applicable approach to estimate prognosis for GBM patients using three objective and readily accessible features: the patient’s age, tumor surface irregularity determined from MRI scans, and the expression of ICAM1 measured by standard immunohistochemistry. We show that higher ICAM1 levels are linked to worse survival and a more inflamed but immunosuppressive tumor microenvironment. These findings are functionally validated in ICAM1-wildtype and knockout mouse models using single-cell proteomics via cytometry by time-of-flight, and an immune-comprehensive panel of antibodies. By combining age, ICAM1, and MRI-derived shape features into a single Clinical-Imaging-Molecular (CIM) score, we developed a model that can reliably separate patients with a GBM into higher- and lower-risk groups. This score was validated across multiple international institutions and patient populations and does not require genomic sequencing or specialized technologies. The CIM model could serve as a supplement for care providers to better tailor treatment plans and follow-up strategies for individual patients, making personalized care more achievable even in resource-limited settings.

Background: Stroke is a devastating complication of transcatheter aortic valve replacement (TAVR). Cerebral embolic protection devices (CEPD) have been introduced to reduce TAVR-related stroke by capturing or deflecting debris during the procedure. While these devices can capture embolic material, their clinical benefit in preventing stroke remains uncertain. We aimed to determine whether the use of CEPD during TAVR reduces the incidence of periprocedural stroke. Methods: We performed a systematic review and meta-analysis of studies comparing TAVR with versus without CEPD. We searched PubMed, Embase, and ClinicalTrials.gov for RCTs (randomized controlled trials) comparing CEPDs to no protection in TAVR patients from 2011 to May 2025. Nine RCTs involving a total of 11,608 patients (CEPD group n=5,953; control n=5,655) were included. Stroke outcomes were defined according to Valve Academic Research Consortium-2 (VARC-2) criteria and categorized as- all stroke, disabling stroke, or non-disabling stroke. Risk ratios (RR) with 95% confidence intervals (CI) were calculated using a fixed-effects model. Heterogeneity also was measured. Results: Stroke rates were low and did not differ significantly between the CEPD (n=343) and control (n=319) groups. The incidence of all strokes was 1.96% with CEPD vs 1.88% without CEPD (RR 0.97, 95% CI 0.75–1.15; p=0.50). Disabling stroke occurred in 0.79% of CEPD patients vs 0.95% of controls (RR 0.79, 95% CI 0.57-1.10; p=0.16). Non-disabling stroke occurred in 1.26% of patients in both groups (RR 1.06, 95% CI 0.8 -1.40; p=0.64). There was no significant heterogeneity across trials is (0) for all endpoints. Notably, the largest trial in the analysis (BHF PROTECT-TAVI, n=7,635) showed no difference in stroke rates with CEPD, aligning with the overall results. Subgroup analyses revealed a trend toward fewer disabling strokes with CEPD use, but this trend was not statistically significant. Conclusion: We found no significant stroke risk reduction with the use of CEPDs during TAVR. While a trend toward fewer disabling strokes was observed, it was not statistically significant. Routine use of CEPDs is not supported, and selective use in high-risk patients warrants further large RCTs.

ABSTRACT We conducted a USA claims‐based cohort study in 20,705 patients with inflammatory bowel diseases (IBD) on advanced therapies to estimate the overall and comparative risk of tuberculosis between advanced therapies using inverse probability of treatment weighted Cox proportional hazards model. The incidence rate (IR, per 100,000 person‐years) of tuberculosis with TNF antagonists ( n = 9378) and non‐TNF‐targeting biologics (anti‐integrins [ n = 5877], anti‐interleukins [ n = 5450]) was similar (38 [95% CI, 8–69] vs. 33[7–59]). Adjusting for covariates, risk of tuberculosis was similar (HR, 1.16 [0.41–3.31]). In low incidence regions like USA, the incidence of tuberculosis after starting advanced therapies for IBD is very low, and comparable across advanced therapies.

INTRODUCTION: We conducted a retrospective cohort study comparing the safety of advanced therapies in patients with ulcerative colitis (UC). METHODS: Using an administrative claims database (OptumLabs Data Warehouse), we identified patients with UC who initiated treatment with tumor necrosis factor-α (TNF) antagonists, anti-integrin agents, anti-interleukin, Janus kinase inhibitors (JAK), or sphingosine-1 phosphate receptor modulators between 2016 and 2022 and had followed up for at least 1 year before and after treatment initiation. We compared the risk of serious infections, venous thromboembolism, and major adverse cardiovascular events through multinomial propensity score-based inverse probability weighting, with propensity scores estimated through generalized boosted models that accounted for disease characteristics, healthcare utilization, comorbidities, and previous and concomitant medications, and the competing risk of mortality. We calculated cause-specific hazard ratios (HR) and 95% confidence intervals for multiple treatment comparisons. RESULTS: We included 9,430 patients with UC treated with TNF antagonists (n = 4,111), anti-integrins (n = 3,165), anti-ILs (n = 1,342), JAK inhibitors (n = 701), or sphingosine-1 phosphate receptor modulators (n = 111), followed over median 27 months. After adjusting for confounding variables, anti-ILs were associated with a lower risk of serious infections compared with TNF antagonists (HR, 0.66 [95% confidence interval, 0.51–0.87]) and anti-integrins (HR, 0.75 [0.57–0.98]). JAK inhibitors were associated with a lower risk of serious infections compared with TNF antagonists (HR, 0.66 [0.46–0.94]). The incidence of venous thromboembolism (incidence rate, 1.4–2.0 per 100 py) and major adverse cardiovascular event (0.5–1.0 per 100 py) was very low, without any significant differences across agents. DISCUSSION: In a real-world cohort of patients with UC, anti-ILs and JAK inhibitors were associated with a lower risk of serious infections and may offer net benefit, especially in patients with previous TNF antagonist exposure.

ABSTRACT Background Advanced therapies increase the risk of shingles in inflammatory bowel diseases (IBD). Aim To compare the risk of shingles with different advanced therapies in patients with IBD. Methods We identified patients with IBD who initiated treatment with tumour necrosis factor (TNF) antagonists, anti‐integrins, anti‐interleukins, Janus kinase (JAK) inhibitors, or sphingosine‐1 phosphate receptor (S1PR) modulators between 2016 and 2022 and had follow‐up for at least 1 year before and after treatment initiation. We estimated the incidence rate (IR per 100 person‐year [PY]) of shingles (overall and complicated) and compared the risk with different advanced therapies through multinomial propensity score‐based inverse probability of treatment weighting (IPTW), with propensity scores estimated through generalised boosted models, accounting for disease characteristics, healthcare utilisation, comorbidities and prior and concomitant medications. Weighted Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for multiple treatment comparisons. Results We included 21,675 patients followed over 27 months. IRs per 100 PY of shingles and complicated shingles were: TNF antagonists 1.0/0.3, anti‐integrin agents 1.4/0.4, anti‐interleukins 1.2/0.5, JAK inhibitors 3.3/0.9 and S1PR modulators 2.0/1.0. After adjusting for confounding variables, JAK inhibitors were associated with higher risks of shingles than TNF antagonists (HR 2.19; 1.28–3.75), anti‐integrins (HR 1.87; 1.12–3.14) and anti‐interleukins (HR 1.70; 0.98–2.96). Conclusions JAK inhibitors were associated with 1.7–2.2‐fold higher risk of shingles than other advanced therapies.

Abstract BACKGROUND Glioblastoma (GBM) is a highly aggressive brain tumour with limited prognostic tools that are broadly implementable in routine clinical settings. Current models often depend on molecular platforms not universally accessible. We aimed to develop and validate a clinically practical prognostic model for GBM that integrates ICAM1 protein expression, imaging-derived tumor morphometrics, and clinical features. MATERIAL AND METHODS We analyzed ICAM1 expression in GBM at the DNA methylation, RNA, and protein levels using public datasets and institutional cohorts, confirming its association with tumor grade and poor survival. ICAM1 protein levels were then quantified via digital pathology in a multi-institutional cohort of 197 newly diagnosed, treatment-naïve GBM patients. Tumor surface irregularity (SIR) was calculated from pre-operative contrast-enhanced MRI using open-source imaging tools. Age at diagnosis was also recorded. These three variables—ICAM1 expression, SIR, and age—were integrated into a Clinical-Imaging-Molecular (CIM) model using multivariable Cox regression. The model was validated in an independent external GBM cohort (n = 20). Survival prediction was assessed using Kaplan-Meier curves, ROC analysis, and concordance index (c-index). RESULTS ICAM1 expression was associated with DNA hypomethylation and significantly correlated with reduced survival at transcriptomic and proteomic levels. Pathway analysis identified associations with immune activation and angiogenesis. In the clinical cohort, high ICAM1 expression, elevated tumor SIR, and older age independently predicted worse survival. The CIM model combining these factors stratified patients into distinct prognostic groups, achieving strong performance (c-index = 0.779, AUC = 0.778). External validation confirmed the model’s predictive utility (median survival difference: 9.1 months, P = 0.009). CONCLUSION We present a validated and clinically applicable prognostic model for GBM that integrates ICAM1 expression, imaging features, and age. The CIM model is scalable, interpretable, and feasible for implementation across academic and community settings, providing a robust tool for patient stratification, treatment planning, and trial design.

Abstract Minimally invasive image-guided tumor ablation techniques have been established as safe, effective methods to treat a variety of unresectable soft tissue tumors. Standard thermal ablation methods include radiofrequency ablation, microwave ablation, and cryoablation. However, newer non-thermal and/or non-invasive ablation techniques are now available as alternative options to treat soft tissue tumors, particularly those that are near critical structures or otherwise susceptible to thermal energy sink effects. The 4 types of emerging ablation techniques discussed in this review are as follows: irreversible electroporation, pulsed electric field, high-intensity focused ultrasound, and histotripsy. While the clinical trials evaluating the safety and efficacy of these ablation techniques are in their early stages, initial results are promising in the treatment of various cancers at different stages. These include potential synergistic effects when combined with chemotherapy and immunotherapy.

Summary We investigated the outcomes of patients with advanced systemic mastocytosis (AdvSM) undergoing allogeneic haematopoietic cell therapy (alloHCT) in the US. Twenty‐seven adult (median age, 58 years) patients with AdvSM received alloHCT from 2014 to 2021. Most patients were white (93%), male (63%) and had systemic mastocytosis (SM) with associated haematological neoplasm (SM‐AHN, 70%), received peripheral blood grafts (89%) and non‐myeloablative regimens. KIT mutation was detected in 14 of the reported 16 patients (87.5%). Post‐transplantation cyclophosphamide (PTCy) was used in approximately 50% of the cohort. Approximately 1 year after alloHCT, median bone marrow mast cell burden decreased from 15% pre‐alloHCT to 1.5% (range 0–8) at 1 year post‐alloHCT. The median serum tryptase decreased from 55 ng/mL (range 3–400 ng/mL) pre‐alloHCT to 18 ng/mL (range 0–481 ng/mL) at 1 year post‐alloHCT. At 1 year, progression‐free survival (PFS) and overall survival (OS) were 59% (95% confidence interval [CI], 41%–77%) and 74% (95% CI, 56%–89%) respectively. In the subset of patients with SM‐AHN, 1‐year PFS and OS were 74% (52%–91%) and 79% (95% CI, 58%–94%) respectively. The cumulative incidence of relapse/progression for the entire population of patients with SM ( n = 27) was 4% (95% CI, 0–14) at 100 days and 15% (95% CI, 4–31) at 1 year. For the subset of patients with AHN, the cumulative incidence was 11% (95% CI, 1–28) at 100 days and 21% (95% CI, 6–42) at 1 year. Relapse/progression was the cause of death in six of 12 patients (5 died of AHN and 1 died of SM progression). Eighteen and nine patients received a KIT inhibitor before alloHCT and after alloHCT respectively. In addition, six patients received a KIT inhibitor for the treatment of relapse/progression of SM after alloHCT. Although it is difficult to delineate the exact effect of alloHCT and KIT inhibitors because of the size of the study in this era, the use of alloHCT and KIT inhibitors pre‐ and post‐ alloHCT is increasing. In the near future, larger studies are required to provide further insights into this subject.

Abstract Obesity is a major and growing driver of cardiovascular disease (CVD) in the United States, contributing to hypertension, diabetes, dyslipidemia, and structural cardiac changes that elevate the risk of ischemic heart disease, heart failure, and stroke. After decades of declining CVD mortality, recent national trends show a concerning reversal, coinciding with record-high obesity prevalence. We quantified national trends and disparities in obesity-related CVD mortality from 1999–2020 using de-identified death certificate data from the CDC WONDER database for U.S. residents aged 15–84 years, including deaths with circulatory disease (ICD-10 I00–I99) as the underlying cause and obesity (E66.0–E66.9) as a contributing cause. Age-adjusted mortality rates (AAMR) standardized to the 2000 U.S. population were analyzed using joinpoint regression to estimate annual percent change (APC) and detect inflection points. From 1999–2018, AAMR rose from 2.75 to 6.61 per 100,000 (APC 4.79%; 95% CI 4.60–4.98), followed by a significant post-2018 acceleration (APC 11.05%; 95% CI 6.76–15.51) to 8.36 in 2020. Mortality was highest among adults 65–74 years, males, Black Americans, and nonmetropolitan residents, with a 5.1-fold state variation. Young adults (15–24 years) had the largest relative increase (+210%). The 2020 surge was independent of COVID-19 mortality, indicating gaps in chronic disease management. These results highlight a growing obesity-related CVD mortality burden, with widening disparities by age, sex, race, and geography, emphasizing urgent, equity-focused prevention and targeted interventions.