Gap junctions have recently been shown to interconnect glioblastoma cells to a multicellular syncytial network, thereby allowing intercellular communication over long distances as well as enabling glioblastoma cells to form routes for brain microinvasion. Against this backdrop gap junction-targeted therapies might provide for an essential contribution to isolate cancer cells within the brain, thus increasing the tumor cells’ vulnerability to the standard chemotherapeutic agent temozolomide. By utilizing INI-0602—a novel gap junction inhibitor optimized for crossing the blood brain barrier—in an oncological setting, the present study was aimed at evaluating the potential of gap junction-targeted therapy on primary human glioblastoma cell populations. Pharmacological inhibition of gap junctions profoundly sensitized primary glioblastoma cells to temozolomide-mediated cell death. On the molecular level, gap junction inhibition was associated with elevated activity of the JNK signaling pathway. With the use of a novel gap junction inhibitor capable of crossing the blood–brain barrier—thus constituting an auspicious drug for clinical applicability—these results may constitute a promising new therapeutic strategy in the field of current translational glioblastoma research.

Emerging evidence emphasizes the prognostic importance of meningioma location. The present investigation evaluates whether progression-free survival (PFS), proliferative potential, World Health Organization (WHO) grades, and inflammatory burden differ between anatomical locations (skull base, non-skull base, and spinal) meningiomas. Five-hundred-forty-one patients underwent Simpson grade I or II resection for WHO grade 1 or 2 meningiomas. Univariable analysis revealed that spinal meningioma patients are significantly older, had a worse baseline Karnofsky Performance Status (KPS), higher acute-phase protein levels, lower incidence of WHO grade 2, lower mitotic counts, lower MIB-1 index, and less CD68⁺ macrophage infiltrates. Multivariable analysis identified WHO grade 2 (OR: 2.1, 95% CI: 1.1–3.7, p = 0.02) and cranial location (OR: 3.0, 95% CI: 1.8–4.9, p = 0.001) as independent predictors of diffuse CD68⁺ macrophage infiltrates. The mean PFS in cranial meningiomas was 115.9 months (95% CI: 107.5–124.3), compared to 162.2 months (95% CI: 150.5–174.0; log-rank test: p = 0.02) in spinal meningiomas. Multivariable Cox regression analysis revealed cranial location as an independent predictor (HR: 4.7, 95% CI: 1.0–21.3, p = 0.04) of shortened PFS. Increased MIB-1 indices ≥5% were significantly associated with location-specific deficits at presentation, such as decreased vision and seizure burden. Spinal meningiomas have a significantly longer PFS time and differ from the cranial meningiomas regarding MIB-1 index and density of tumor-associated macrophages.

Background: Although the initial functional outcome findings of the International Subarachnoid Aneurysm Trial (ISAT) study favored coiling at one year after aneurysmal subarachnoid hemorrhage (aSAH), concerns arose regarding limited long-term rerupture data. This meta-analysis is the first to analyze longitudinal individual patient data (IPD) of target aneurysm rerupture in terms of treatment modality. Methods: The present meta-analysis included studies that compared clipping with coiling of ruptured aneurysms regarding long-term rerupture. Rerupture rates’ individual patient data (IPD) were extracted from published Kaplan–Meier curves utilizing the R package IPDfromKM in R Version 4.3.1. Results: A total of 3153 patients from two studies were included. The clipping arm included 1755 patients, whereas the coiling arm included 1398 patients. Median reconstructed follow-up was 6.1 years (IQR = 0.5–11.7). The rerupture rates in the clipping arm and the coiling arm were 0.5% and 1.5%, respectively (p = 0.002). Kaplan–Meier chart analysis of the 3153 patients revealed a shortened time to rerupture in the coiling arm (log-rank test: p = 0.01). The hazard ratio (HR) for coiling compared with clipping regarding rerupture was 3.62 (95% CI:1.21–10.86, p = 0.02). Conclusion: Target aneurysm rerupture was rare beyond the initial year. Pooled long-term IPD from the 3153 patients revealed that reruptures of target aneurysms are more common after coiling and might be considered in the pretherapeutic decision-making process for aSAH.

Delayed cerebral ischemia (DCI) is a predictor of poor outcome after aneurysmal subarachnoid hemorrhage (SAH). Treatment strategies vary and include induced hypertension and invasive endovascular treatment. After the IMCVS trial (NCT01400360), which failed to demonstrate a benefit of endovascular treatment for cerebral vasospasm (CVS) and resulted in a significantly worse outcome, we changed our treatment policy in patients with diagnosed CVS to induced hypertension only, and we present our prospective results in the subgroup of SAH patients meeting inclusion criteria of the IMCVS trial. All patients underwent screening for DIND when conscious and for CVS using CT-A/-P at day 6–8 after SAH. In the case of CVS, arterial hypertension was induced and continued until re-assessment. In total, 149 of 303 patients developed CVS. DCI developed in 35 patients (23.5%). In multivariate analyses, CVS was a predictor for the development of new infarctions. Poor admission status, re-bleeding before treatment, and DCI predicted poor outcome. The omittance of invasive endovascular rescue therapies in SAH patients with CVS, additional to induced hypertension, does not lead to a higher rate of DCI. Potential benefits of additional endovascular treatment for CVS need to be addressed in further studies searching for a subgroup of patients who may benefit.

The MIB-1 index is an essential predictor of progression-free-survival (PFS) in meningioma. To date, the MIB-1 index is not available in preoperative treatment planning. A preoperative score estimating the MIB-1 index in patients with intracranial meningiomas has not been investigated so far. Between 2013 and 2019, 208 patients with tumor morphology data, MIB-1 index data, and plasma fibrinogen and serum C-reactive protein (CRP) data underwent surgery for intracranial WHO grade I and II meningioma. An optimal MIB-1 index cut-off value (≥6/<6) in the prediction of recurrence was determined by ROC curve analysis (AUC: 0.71; 95% CI: 0.55–0.87). A high MIB-1 index (≥6%) was present in 50 cases (24.0%) and was significantly associated with male sex, peritumoral edema, low baseline CRP, and low fibrinogen level in the multivariate analysis. A scoring system (“FORGE”) based on sex, peritumoral edema, preoperative CRP value, and plasma fibrinogen level supports prediction of the MIB-1 index (sensitivity 62%, specificity 79%). The MIB-1 labeling index and the FORGE score are significantly associated with an increased risk of poor PFS time. We suggest a novel score (“FORGE”) to preoperatively estimate the risk of an increased MIB-1 index (≥6%), which might help in surgical decision making and follow-up interval determination and inform future trials investigating inflammatory burden and proliferative activity.

Emerging evidence suggests that neuroinflammation may play a potential role in aneurysmal subarachnoid hemorrhage (aSAH). We aim to analyze the influence of anti-inflammatory therapy on survival and outcome in aSAH. Eligible randomized placebo-controlled prospective trials (RCTs) were searched in PubMed until March 2023. After screening the available studies for inclusion and exclusion criteria, we strictly extracted the main outcome measures. Dichotomous data were determined and extracted by odds ratio (OR) with 95% confidence intervals (CIs). Neurological outcome was graded using the modified Rankin Scale (mRS). We created funnel plots to analyze publication bias. From 967 articles identified during the initial screening, we included 14 RCTs in our meta-analysis. Our results illustrate that anti-inflammatory therapy yields an equivalent probability of survival compared to placebo or conventional management (OR: 0.81, 95% CI: 0.55–1.19, p = 0.28). Generally, anti-inflammatory therapy trended to be associated with a better neurologic outcome (mRS ≤ 2) compared to placebo or conventional treatment (OR: 1.48, 95% CI: 0.95–2.32, p = 0.08). Our meta-analysis showed no increased mortality form anti-inflammatory therapy. Anti-inflammatory therapy in aSAH patients tends to improve the neurological outcome. However, multicenter, rigorous, designed, prospective randomized studies are still needed to investigate the effect of fighting inflammation in improving neurological functioning after aSAH.