Wilco Cornelis Peul

Background: Brain tumors cause more than 248 000 deaths annually, and their incidence continues to rise. Despite medical advances, outcomes have improved marginally, and the associated economic burden is substantial. European spending was estimated at €37.8 billion in 2019. Although several cost drivers have been identified, robust and methodologically sound cost evaluations remain limited. This study aimed to quantify 30-day in-hospital healthcare consumption and identify cost drivers in brain tumor surgery. Methods: Adult patients undergoing brain tumor surgery in 2023 at a single regional referral center were retrospectively analyzed. The primary outcome was total 30-day in-hospital costs, calculated using a bottom-up microcosting approach. Univariable and multivariable analyses were performed to identify key cost drivers. Results: A total of 322 patients (mean age 61 years; 51.2% female) were included in this study. Median length of stay (LOS) was 3 days (interquartile range; 2-6), and mean in-hospital costs were € 6988 per patient (SD ± € 4273). Tumor pathology was associated with significantly increased surgical costs (P = .035) but did not significantly influence overall costs (P = .376). Multivariable analysis identified surgery type, preoperative Karnofsky Performance Status, total LOS, intensive care unit LOS, and Clavien-Dindo complication grade as independent cost drivers. Repeat surgery, readmission, and 30-day mortality further increased costs. Conclusions: Thirty-day in-hospital costs following brain tumor surgery are substantial, mainly driven by operative and hospitalization factors. Identifying modifiable cost determinants is essential for developing targeted interventions to improve efficiency and optimize resource utilization.

High-quality evidence to guide the practice of acute cranial surgery across age groups in traumatic brain injury (TBI) remains sparse. Current surgical guidelines generally do not consider age in their recommendations. The aim of the study is to evaluate acute cranial surgery rates and center treatment differences across age in TBI. Data were extracted from the prospective observational Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) study. The CENTER-TBI study included patients with TBI between 2014 and 2017 from 65 level 1 trauma centers across Europe and Israel. Data from all 27,358 patients with TBI enrolled in the CENTER-TBI core study ( n = 4509) and registry ( n = 22,849) were considered. Eight patients with missing age were excluded, leading to a final analytic sample of 27,350 (core study n = 4504, registry n = 22,846). Variations in probability, defined as case-mix adjusted proportions, of acute surgical treatment of intracranial mass effect (primary decompressive craniectomy or craniotomy), performed within 24 h of initial injury, were expressed using median odds ratios (MORs). Adjusted odds ratios (aORs) were calculated using random-effects linear regression to assess the association between age and the probability of acute cranial surgery for acute subdural hematoma, epidural hematoma, or intracerebral hemorrhage/contusions. MORs and aORs were reported with 95% confidence interval (CI). The odds of acute surgery decreased with older age (aOR = 0.93, 95% CI: 0.92–0.95, per each interquartile range increase of 37 years [y]). Variations in center-specific surgery rates increased with age (15–24 y: MOR = 1.4; 25–44 y: MOR = 1.5; 45–64 y: MOR = 1.6; 65–79 y: MOR = 1.8; ≥80 y: MOR = 3.3), except for patients aged <15 y (MOR = 2.9). Older patients with TBI were less likely to receive acute cranial evacuation surgery, independent from other (comorbidity) factors. Higher age was associated with more surgical treatment variation between centers. Neurosurgery for TBI can be improved by age-personalized treatment algorithms.

Chordomas are ultra-rare cancers from the axial skeleton with limited treatment options. Chordomas can exhibit immunogenic features, and immune checkpoint blockade has demonstrated clinical activity in some patients, yet the determinants of these responses remain poorly understood. We aimed to elucidate the biological basis of immunogenicity in chordomas through spatial transcriptomic and metabolomic analyses. We applied GeoMx digital spatial profiling to 15 chordomas, analyzing tumor and stromal compartments separately and comparing inflamed and non-inflamed tumors. Consecutive tissue sections were examined using MALDI-mass spectrometry imaging (MSI) at 20 µm spatial resolution. Findings were further explored through immunohistochemistry analyses. To assess whether transcriptional activity in tumor cells was associated with interferon-γ (IFN-γ) signaling, we tested the effect of IFN-γ treatment on chordoma cell lines. Digital spatial profiling of inflamed and non-inflamed chordomas revealed striking differences in both the cancer cell and stromal compartments. Increased immune infiltration was strongly associated with elevated transcriptional activity in cancer cells. MALDI-MSI revealed distinct metabolic signatures and pronounced glycogen accumulation in inflamed chordomas. Nevertheless, IFN-γ stimulation of chordoma cell lines did not induce expression of TBXT (brachyury), the master transcriptional regulator of chordoma biology. Collectively, our findings reveal a strong association between the transcriptomic and metabolic activity in chordomas and their immunogenicity. However, the causal direction of this relationship remains to be determined. Nevertheless, these findings are highly relevant for patient stratification, particularly in the context of immunotherapeutic strategies.

Purpose: Both the Glasgow Coma Scale (GCS) and Abbreviated Injury Scale (AIS) for head injuries quantify traumatic brain injury (TBI) severity. The GCS is based on brain physiology of consciousness, whereas the AIS is an anatomical injury scoring system. This study aimed to describe the correlation of GCS with maximal AIS-Head (maxAIS) and summative AIS-Head (sumAIS) in TBI patients. Methods: Data of 4996 adult TBI patients admitted to two level 1 trauma centers in the Netherlands between 2015 and 2021 were selected from the regional trauma registry. The association of GCS with maxAIS and sumAIS was quantified using Spearman rank correlation coefficients (r _s ). Results: For 39% of the patients, the GCS was not documented in the trauma registry. These patients had less severe head injuries than the 3051 patients with documented GCS scores, who were further analyzed. Among those with severe head injuries (AIS-Head ≥ 4), 53% had a GCS score ≥ 13. The GCS showed a weak inverse relationship with both maxAIS and sumAIS (r _s -0.33 and − 0.34, respectively, both p < 0.001). Conclusions: The correlation between physiological alterations (GCS) and anatomical brain damage (AIS) in patients with TBI patients, represented by the GCS and AIS respectively, is weak. Additionally, the GCS appears to underestimate the severity of AIS coded severe TBI. Recognizing this limited correlation is important for valid TBI research.

To compare the incremental prognostic value of pupillary reactivity captured as part of the Glasgow Coma Scale-Pupils (GCS-P) score or added as separate variable to the GCS+P, in traumatic brain injury (TBI). We analyzed patients enrolled between 2014 and 2018 in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI, n = 3521) and the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI, n = 1439) cohorts. Logistic regression was utilized to quantify the prognostic performances of GCS-P (GCS minus number of unreactive pupils) and GCS+P versus GCS alone according to Nagelkerke's R². End-points were mortality and unfavorable outcome (Glasgow Outcome Scale-Extended score 1-4) at 6 month post-injury. We estimated 95% confidence intervals (CIs) with bootstrap resampling to summarize the improvement in prognostic capability. In a meta-analysis of CENTER-TBI and TRACK-TBI, GCS as a linear score had a R² of 25% (95% CI 19-31%) for mortality and 33% (4-41%) for unfavorable outcome. Pupillary reactivity as a separate variable improved the R² by an absolute value of 6% (4.0-7.7%) and 2% (1.2-3.0%) for mortality and unfavorable outcome, respectively, while comparatively half of this improvement was captured by the GCS-P score (3% [2.1-3.3%], 1% [1-1.7%], respectively). GCS-P showed a stronger association with 6-month outcome after TBI than GCS alone and provides a single integrated score. However, this comes at a loss of clinical and prognostic information compared with GCS+P. For prognostic models, inclusion of GCS and pupillary reactivity as separate factors may be preferable to using a GCS-P summary score.

Objectives: Determine the incidence, location, and features of insufficiency fractures (IFs) in sacral chordoma patients treated with high-dose radiation therapy (HDR) with(out) resection, relative to radiation therapy type and irradiation plans. Methods: Clinical data, including details of all surgical procedures and radiotherapies of patients histologically diagnosed with sacral chordoma between 2008 and 2023 available at our database, were retrospectively reviewed. Inclusion criteria were as follows: availability of diagnostic, treatment planning and follow-up magnetic resonance and/or computed tomography scans, and completed treatment. Scans were re-evaluated for the presence and location of IF defined as linear abnormalities with(out) bone marrow oedema (BME)-like changes. Results: From 48 included patients (29 male, median age 66, range 27-85), 22 were diagnosed with 56 IF (45.8%). IF occurred 3-266 months following the treatment. All sacral and iliac bone IF had vertical components parallel to the SI joint. Twenty patients had bilateral and 16 unilateral IF. BME-like changes were visible in 46 IF (82.1%, 0.80, P ≤ .001). In 13/56 IF (23.2%), BME-like changes were seen prior to IF diagnosis; in only 1 patient, BME-like changes did not develop into an IF. Thirty-nine IF (84.7%) occurred within low-dose volume and 7 (15.3%) outside of irradiated volume in 16/44 irradiated patients. Six IF occurred in 1 patient treated with surgery only. Conclusions: Pelvic IFs are common in sacral chordoma patients treated with definitive or (neo)adjuvant HDR, occurring months to years following treatment. Not all IF occur in the irradiated volume. Advances in knowledge: When present, BME-like changes indicate risk of IF developing. IF do not heal over time.

Traumatic brain injury (TBI) is a major global health and socioeconomic problem affecting more than 50 million people each year and causing an estimated global financial burden of USD 400 billion [1]. Low-income and middle-income countries (LMICs) are disproportionately impacted, as about 90% of trauma-related deaths worldwide occur in such contexts [2]. In India, approximately […]