Citations

Abstract Background Astroblastomas are rare brain tumors predominantly affecting children and young adults, for which molecular subtypes and clinical management remain undefined. Methods We analyzed tumor samples, molecular profiles, and clinical data from 200 patients, classified as “Astroblastoma, MN1-altered” under WHO criteria, using DNA methylation profiling, DNA/RNA profiling/sequencing, and survival analyses. Results DNA methylation analyses identified 3 groups: Group A (n = 143, characterized by MN1::BEND2 fusions, predominantly supratentorial location, with striking female predominance and favorable survival); Group B (n = 37, epigenetically and transcriptionally closely related to Group A, but characterized by EWSR1::BEND2 fusions, with spinal and infratentorial locations and poor prognosis); and Group C (n = 20, epigenetically and transcriptionally distinct, characterized by MN1::CXXC5 fusions, exclusively supratentorially located, with favorable survival). Progression-free and overall survival were significantly shorter in Group B (5-year PFS 14%; 10-year OS 54%) compared to A (5-year PFS 47%; 10-year OS 89%) and C (5-year PFS 75%; 10-year OS 89%). Radiotherapy improved PFS in Group B (hazard ratio 0.25), while no clear benefit was identified for Groups A and C. Conclusions Astroblastoma, MN1-altered, comprises 3 molecularly and clinically distinct groups, characterized by different fusion genes, including those without MN1. These new insights, including the identification of potential predictive biomarkers like 14q/16q loss, provide a framework for the development of risk-stratified therapeutic approaches. Importantly, we identified a molecularly defined high-risk group that benefits from radiation therapy. Our findings redefine Astroblastoma as a molecularly diverse tumor type, propose a refined classification, support the development of risk-adapted therapeutic strategies and provide a rational standard of care.

PURPOSE To compare patient-reported and clinical outcomes between radical cystectomy (RC) and bladder-sparing therapy (BST) in patients with recurrent high-grade non–muscle-invasive bladder cancer (NMIBC). PATIENTS AND METHODS This pragmatic, prospective observational cohort study was designed with patients, who selected and prioritized outcomes. Eligible adults were candidates for both RC or BST, had previous induction Bacillus Calmette-Guérin (BCG), and received their last treatment within 12 months. The primary outcome was the EORTC-QLQ-C30 physical function scale at 12 months. Secondary outcomes included other EORTC-QLQ-C30 scales, depression, anxiety, bladder cancer–specific quality of life (QOL), financial burden, and cancer-specific outcomes. Targeted maximum likelihood estimation (TMLE) was used to calculate average treatment effect (ATE) estimates between arms. Inverse probability weighted risk ratios (wRR) were calculated using quasi-Poisson regression. RESULTS Of 570 participants (mean age 71.4 years; 21% female), 371 selected BST and 199 selected RC. Physical function was significantly worse in the RC arm at 3 months; by 9 months, there was no difference between arms, and at 12 months, physical function did not differ (ATE, 0.9; 95% CI, –0.6 to 2.4; P = .22). RC was associated with better emotional function, generic health-related QOL, and financial burden, and lower depression and anxiety, while BST was associated with better bowel and sexual health. Cancer-specific survival was 99% for BST versus 96% for RC (wRR, 0.99; 95% CI, 0.97 to 1.01). RC was associated with a higher risk of adverse events and serious adverse events, including a 90-day mortality rate of 2.5%. CONCLUSION Most patient-prioritized outcomes were similar or better among participants who chose RC compared with BST. These findings support the continued role of RC in managing recurrent high-grade NMIBC.

Abstract There are no approved treatments for relapsed/refractory (R/R) PCNSL. We show promising efficacy in the salvage setting using emavusertib in combination with ibrutinib, which targets the BCR and TLR pathways. These 2 major pathways are associated with activation of NF-κB. Updated safety and efficacy data of this combination in R/R PCNSL from the ongoing Phase 1/2 TakeAim Lymphoma trial (NCT03328078) will be presented. As of 01 May 2025, 33 patients with R/R PCNSL were treated with emavusertib in combination with ibrutinib. Eligible patients receive emavusertib in combination with ibrutinib until tumor progression or unacceptable toxicity. Median age was 63 years (range 43-81); 16 patients were male. Median prior anti-cancer therapy was 2 (range 1-5); 26 (78.8%) patients had prior BTKi exposure. Median duration of emavusertib/ibrutinib treatment was 51 days (range 5-798). Grade ≥ 3 treatment-related adverse events (TRAEs) were reported in 11 (33.3%) patients; neutropenia in 5 (15.2%) patients, amylase increased, lipase increased, and leukopenia in 2 (6.1%) patients each. The majority of Grade ≥ 3 TRAEs were reversible and manageable. Among the 19 BTKi-experienced patients treated for ≥ 28 days, there were 5 CRs and 2 PRs, with an ORR of 36.8%. Three patients with CR were on treatment for 10+ mos, with 1 CR patient ongoing with DOT of 26.2+ mos. Among the 5 BTKi-naïve patients treated for ≥ 28 days, 1 achieved CR and 3 had PR, with ORR of 80%; the CR patient is ongoing with DOT of 18.1+ mos. The ORR in the combined population was 45.8% (6 CRs; 5 PRs). The combination of emavusertib and ibrutinib demonstrates promising clinical activity and an acceptable safety profile in patients with R/R PCNSL. This regimen appears capable of overcoming resistance to prior BTKi therapy. Patient enrollment in this trial continues.

Abstract PCNSL is a rare and aggressive NHL with no approved treatments for R/R patients, representing a critical unmet need. MyD88 mutations in ~70% of PCNSL patients drive IRAK4 activation, promoting NF-κB signaling, inflammation, and tumor progression. Emavusertib, a potent oral IRAK4 inhibitor, crosses the blood-brain barrier and shows preclinical synergy with BTKis, and has the ability to re-sensitize BTKi-resistant cell lines. This study evaluates the molecular and PK data associated with responses to emavusertib + ibrutinib combination therapy in R/R PCNSL patients. The safety, clinical activity, and potential biomarkers of emavusertib in R/R PCNSL are being investigated in the ongoing TakeAim Lymphoma trial (NCT03328078). Pre-dose and 1.5-hour post-dose plasma samples were collected on Day 1 of Cycles 3, 5, and 7. CSF samples were obtained via a lumbar puncture within 1.5 hrs of collection of the post-dose plasma PK sample on Cycle 3 Day 1. As of 06 December 2024, CSF concentration was available for 7 patients. The mean emavusertib concentration in CSF was 81.3 ng/ml (54.7-104.0) in patients receiving 100 mg emavusertib BID (n=4). In patients receiving 200 mg emavusertib BID (n=3), the mean emavusertib concentration in CSF was higher at 175.7 ng/ml (114.8-209.4), which is 2.2 × the mean value in patients who received 100 mg emavusertib BID (p-value = 0.02). MyD88 mutation status was available for 7 patients of which all had prior BTKi exposure. Among these patients, 6 had MyD88 mutations of which 4 had responded (3 CRs and 1 PR) to the combination with DOR up to 18.9 mos with data collection ongoing. Preliminary CNS PK data demonstrate that emavusertib concentration in CSF increases with increasing emavusertib dose. Patients with MyD88 mutations showed expected promising preliminary efficacy to emavusertib + ibrutinib combination and may overcome BTKi resistance. Enrollment is ongoing.

Objective: Vestibular schwannomas (VSs) treated with stereotactic radiosurgery (SRS) often show transient loss of central tumor enhancement. We hypothesized that this loss of enhancement may correlate with better tumor control on follow-up imaging. Methods: We evaluated 198 consecutive patients from a single center who met eligibility criteria. Tumor volumes on the pre-SRS and post-SRS scans were quantified along with regions of loss of enhancement on the first post-SRS study. The latter was correlated with tumor volumes at follow-up, radiation isocenter density, and loss of serviceable hearing. Results: For the entire cohort, the median loss of enhancement on the first post-SRS scan was 14% (IQR: 6 to 25) and median rate of change in tumor volume was −4.5% per year (IQR: −10.5 to 1.5). Percent loss of central enhancement showed significant negative correlation with tumor growth not only for the entire cohort (correlation coefficient: −0.18, P =0.01), but also for the subset of patients who had available imaging until at least 2 years (n=185) and 4 years (n=179) post-SRS. Loss of enhancement also strongly correlated positively with tumor volumes and number of radiation isocenters and negatively with isocenter density. Finally, patients with greater percent loss of enhancement had an increased likelihood of progression to non-serviceable hearing, although this association was not statistically significant. Conclusions: These findings suggest that loss of central tumor enhancement in VSs post-SRS may be associated with improved tumor control.

Background: The prevalence of cardiac implantable electronic devices (CIED) is increasing, with over 300,000 new implants annually in the U.S. Stress cardiac magnetic resonance (CMR) has proven as a powerful modality for myocardial characterization, enabling accurate diagnosis of different cardiac conditions. In patients without devices, CMR findings have also demonstrated prognostic value for major adverse cardiovascular events (MACE) and guide clinical decision-making. However, its use in CIED patients has historically been limited due to safety and image quality concerns. Hypothesis: We aimed to evaluate the prognostic value of CMR imaging using wideband sequences in CIED patients. Methods: CIED patients referred for clinical CMR were included prospectively and retrospectively between January 2020 and February 2025. All patients underwent a stress CMR protocol, which included cine, wideband late gadolinium enhancement (LGE), wideband T1 mapping, and wideband stress/rest perfusion imaging. Clinical follow-up is ongoing. The primary endpoint was the occurrence of MACE, defined as the composite of myocardial infarction, heart failure hospitalization, implantable cardioverter defibrillator (ICD) therapy, cardiac death, revascularization, or heart transplant. Results: A total of 89 patients were included (median age 69.0 [58.0–75.5] years; 62.9% male). Device types included pacemakers (33.7%), ICDs (48.3%), and cardiac resynchronization therapy devices (16.9%). Over a median of follow-up of 613 days [355-991], 21 patients experienced a MACE. In unadjusted models, higher left ventricular ejection fraction (LVEF) (per 5%) was significantly associated with a lower risk of MACE (odds ratio [OR] 0.80, 95% confidence interval [CI] 0.65–0.95; p=0.016), as was higher stress myocardial blood flow (MBF) (per 0.25 mL/g/min increase: OR 0.78, 95% CI 0.60–0.98; p=0.05). In contrast, greater LV myocardial mass (per 10 g) was significantly associated with a higher risk of MACE (OR 1.27, 95% CI 1.08–1.52; p = 0.006), figure 1. Conclusion: The use of wideband sequences enabled the assessment of prognostic imaging value in CIED patients. LVEF remains a strong and consistent predictor of MACE in this population and LV mass was significantly associated with higher rates of MACE reflecting the influence of underlying cardiomyopathy. While stress perfusion CMR imaging showed promising trends, further studies with longer follow-up are needed to clarify its prognostic value in this population.

Background Carpal tunnel release (CTR) is one of the most frequently performed procedures in the United States, with both open (OCTR) and endoscopic (ECTR) techniques widely used. As surgical practices evolve and outpatient care expands, understanding future utilization trends across care settings is increasingly important. This study projects the use of OCTR and ECTR through 2040 to inform shifting surgical preferences and healthcare demands. Methods This study analyzed procedural data from 2010 to 2019 using the PearlDiver Mariner all-payer claims database. Cases of OCTR and ECTR were identified using Current Procedural Terminology codes. Procedures were further stratified by inpatient or outpatient status based on the documented site of service field within the database. Log-linear, Poisson, negative binomial regression, and autoregressive integrated moving average (ARIMA) models were applied to procedural volumes to project trends through 2040. The ARIMA model was selected based on the lowest normalized root mean square error and overall model performance. Results In 2019, there were 31,190 outpatient ECTR, 155 inpatient ECTR, 101,334 outpatient OCTR, and 1359 inpatient OCTR procedures. By 2040, outpatient ECTR is projected to grow to 65,072 cases (95% CI, 62,471–67,781) at 3.79% annually. Inpatient ECTR is projected to reach 181 cases (95% CI, 97–340) with 2.13% annual growth. Outpatient OCTR is expected to decline to 77,834 cases (95% CI, 76,287–79,413), and inpatient OCTR to 962 cases (95% CI, 809–1143), with annual decreases of 1.19% and 1.48%, respectively. Conclusions By 2040, demand for outpatient ECTR is projected to increase by 110.31% compared to 2019, whereas outpatient OCTR is expected to decline by 20.31%. Although inpatient utilization remains limited, the adoption of endoscopic techniques is anticipated to rise across all care settings, in contrast to the continued decline of open procedures. These trends highlight the ongoing shift toward minimally invasive, ambulatory surgical care. Strategic planning in surgical training, healthcare infrastructure, and reimbursement models will be critical to meet changing demands. Further research is needed to validate these projections in broader populations and across diverse healthcare systems.

Purpose Genitourinary syndrome of menopause (GSM) describes the symptoms and physical changes that result from declining estrogen and androgen concentrations in the genitourinary tract during the menopausal transition. This guideline provides information to clinicians regarding identification, diagnosis, counseling, and treatment for patients with GSM to optimize symptom control and quality of life while minimizing adverse events. Methods The systematic review used in the creation of this guideline is based on research conducted by the Minnesota Evidence-based Practice Center (EPC) under contract to the Agency for Healthcare Research and Quality and funded by the Patient Centered Outcomes Research Institute. The EPC synthesized effectiveness and/or harms outcomes from 68 publications. An additional 66 articles evaluating 46 nonhormonal interventions were described in an evidence map. Results Clinicians diagnose GSM based on symptoms, with or without related physical findings, and after ruling out other etiologies or co-occurring pathologies. There is a large body of evidence examining the use of hormonal and nonhormonal treatment options to manage the symptoms of GSM; however, the local low-dose vaginal estrogen has the most robust evidence base. Conclusion The strategies defined in this document were derived from evidence-based and consensus-based processes. Given that there is insufficient information to recommend one hormonal therapy over another, this guideline is not meant to support a stepwise progression through different hormonal approaches. The clinician should make treatment decisions in the context of shared decision-making, considering patient goals and preferences, using the evidence of efficacy and adverse events of each possible intervention as a guide.

Aberrant internal carotid arteries (ICA) are congenital vascular anomalies that occur from involution of the cervical portion of the ICA, which leads to enlargement of the normally small collateral inferior tympanic and caroticotympanic arteries. The inferior tympanic artery is a branch of the external carotid artery, usually the ascending pharyngeal artery, which extends through the inferior tympanic canaliculus (ITC), a small foramen located along the cochlea promontory. Aberrant ICAs can also be associated with a persistent stapedial artery (PSA), which is an abnormal vessel that arises from the petrous ICA and passes through the obturator foramen of the stapes. An aberrant ICA is a very important anomaly to recognize on imaging. Accurately describing its presence is important to help prevent iatrogenic injury during intervention. It is also important to distinguish an aberrant ICA from a lateralized ICA. The improvement of spatial resolution with photon counting detector (PCD)-CT has been proven to provide higher performance in detection of sub-centimeter vascular lesions compared to conventional energy-integrated detector (EID)-CT. PCD-CT also provides superior visualization of small skull-based foramina such as the inferior tympanic canaliculus, which can aid in more accurately characterizing an aberrant ICA (variant course without ITC involvement).

Key Points In individuals undergoing bariatric surgery, the magnitude of decline in GFR postbariatric surgery is directly associated with presurgery GFR. Reductions in GFR postsurgery were only weakly correlated with weight loss. In obese individuals, GFR-estimating equations performed best when deindexed and when applied in people with reduced kidney function. Background Important questions remain about how bariatric ( i.e ., weight loss) surgery affects measured GFR (mGFR) and eGFR as well as what factors influence change in mGFR postsurgery. Methods Data were pooled from all seven available studies (dates: 2004–2018) measuring GFR prebariatric and postbariatric surgery using gold standard methods. Change in postsurgery mGFR, factors that could influence change in mGFR, and effects on five GFR-estimating equations were analyzed using standard statistical methods. Results The cohort included 105 individuals from the United States and Europe. Sixty-eight percent were female, 97% were White, the mean age was 50 years (range, 24–70), and the mean body mass index was 46±8 kg/m 2 . The mean presurgery mGFR of 107 ml/min (range, 31–215) fell to 92 ml/min (−14%; 95% confidence interval, −21 to −10) postsurgery, with a strong linear relationship existing between presurgery mGFR and % change in GFR ( r =−0.51; −0.64 to −0.35). Individuals with presurgery mGFR ≥90, 60 to <90, and<60 ml/min had −25 (−32 to −19), 1 (−11 to 13), and 7 (0 to 14) ml/min mean postoperative changes in mGFR. Change in weight was significantly correlated with change in mGFR ( r =0.22; 0.03 to 0.40). After adjusting for sex, changes in mGFR postsurgery were associated with higher presurgical age (−0.6 ml/min per year; −1.1 to −0.2), mGFR (−0.5 ml/min per 1 ml/min; −0.6 to −0.4), and change in systolic BP (−0.3 ml/min per 1 mm Hg; −0.6 to 0.0). All GFR-estimating equations significantly underestimated postsurgical GFR reductions in people with preserved kidney function and had improved bias, precision, and accuracy when deindexed and applied to individuals with mGFR <90 ml/min. Conclusions In individuals with obesity undergoing bariatric surgery, the magnitude of postsurgical decline in mGFR was directly associated with presurgery GFR and weakly correlated with weight loss. In addition, GFR-estimating equations' performance improved when deindexed and used in people with reduced kidney function, with the combined creatinine/cystatin C equations having the best overall performance.