In recent years, PD-1/PD-L1 immune checkpoint inhibitors have improved cancer therapy in many tumor types, but no benefit of immune checkpoint therapy has been found in glioblastoma multiforme (GBM). Based on the results of our earlier work, which showed a reduction of PD-L1 expression in patients treated with temozolomide (TMZ), we aimed to investigate the link between TMZ therapy and the immune control point target PD-L1. RNA-sequencing data from de-novo and recurrent glioblastoma were analyzed by AutoPipe algorithm. Results were confirmed either in a cell model by two primary and one established GBM cell line and specimens of de-novo and recurrent GBM. PD-L1 and pathway activation of the JAK/STAT pathway was analyzed by quantitative real-time PCR and western blot. We found a significant downregulation of the JAK/STAT pathway and immune response in recurrent tumors. The cell model showed an upregulation of PD-L1 after IFNγ treatment, while additional TMZ treatment lead to a reduction of PD-L1 expression and JAK/STAT pathway activation. These findings were confirmed in specimens of de-novo and recurrent glioblastoma. Our results suggest that TMZ therapy leads to a down-regulation of PD-L1 in primary GBM cells. These results support the clinical findings where PD-L1 is significantly reduced in recurrent GBMs. If the target is diminished, it may also lead to impaired efficacy of PD-1/PD-L1 inhibitors such as nivolumab.

Although reactive astrocytes constitute a major component of the cellular environment in glioblastoma, their function and crosstalk to other components of the environment is still poorly understood. Gene expression analysis of purified astrocytes from both the tumor core and non-infiltrated cortex reveals a tumor-related up-regulation of Chitinase 3-like 1 (CHI3L1), a cytokine which is related to inflammation, extracellular tissue remodeling, and fibrosis. Further, we established and validated a co-culture model to investigate the impact of reactive astrocytes within the tumor microenvironment. Here we show that reactive astrocytes promote a subtype-shift of glioblastoma towards the mesenchymal phenotype, driving mitogen-activated protein kinases (MAPK) signaling as well as increased proliferation and migration. In addition, we demonstrate that MAPK signaling is directly caused by a CHI3L1-IL13RA2 co-binding, which leads to increased downstream MAPK and AKT signaling. This novel microenvironmental crosstalk highlights the crucial role of non-neoplastic cells in malignant brain tumors and opens up new perspectives for targeted therapies in glioblastoma.

Chronic subdural hematoma (cSDH) is prevalent in the elderly, frail, and those on antithrombotic therapy, often resulting in significant morbidity and mortality. Recurrence and reoperation rates are substantial concerns. Emerging evidence suggests that irrigation, drainage, and possibly fibrinolytic therapy, may improve reoperation rates. To explore safety and efficacy of twist-drill craniostomy (TDC) with pressure-controlled fibrinolytic irrigation therapy (TDC-FIT) in reducing recurrence rates of cSDH compared to conventional TDC with subdural passive drainage. A retrospective study included 314 patients treated with TDC and 16 patients treated with TDC-FIT between January 2021, and March 2024. The primary endpoint was the reoperation rate due to symptomatic recurrence or persistence of cSDH at 6 months. Secondary endpoints included hematoma resolution, perioperative complications, and the impact of antithrombotic therapy and preoperative membrane formation. Reoperation was required in 107 (34.1 %) TDC patients and in one (6.3 %) TDC-FIT patient (P = .026). Hematoma membranes (OR 2.6, 95 % CI 1.6-4.3, P < .001) and dual antithrombotic therapy (OR 10.3, 95 % CI 1.1-93.3, P = .041) were significantly associated with reoperation in the TDC cohort. TDC-FIT showed superior hematoma resolution with a similar complication profile and functional outcome. TDC-FIT patients had a significantly lower reoperation rate despite a higher presence of hematoma membranes (75 % vs. 34.7 %, P = .002). Preliminary data on TDC-FIT suggests improved reoperation rate and membranous hematoma resolution with comparable safety profiles to conventional TDC. Further prospective studies are needed to validate these findings in larger cohorts.

Summary: We report on a case of a trans-man patient, who underwent penile reconstruction with the use of a radial forearm flap, urethroplasty, vaginectomy and scrotoplasty, insertion of testicle implants, and penile erection implants, similar to previously described methods. One of the requirements for an ideal phalloplasty is the preservation of erogenous sensitivity, which is often demanded by the patients for fulfilling their sexual well-being. For the first time known to us, we use a functional magnetic resonance imaging following radial forearm flap phalloplasty with nerve anastomosis to assess the cortical activation after clitoral stimulation. The patient was poked with a plastic pen on the neophallus and the groin. Regular block design with T1 and BOLD-T2* images were used. The results contradict the classic Penfield and Rasmussen homunculus, that is, the activations in the primary somatosensory cortex (S1) were bilateral with a left-sided dominance in the lateral parts of the medial postcentral gyrus (same region as the groin), and no activations were observed in the mesial parts of the postcentral gyrus. We also reported bilateral activations with a left-sided dominance in the secondary somatosensory cortex (S2) and near Broca’s area at the sylvian fissure just posterior to ramus ascendens. Our findings are similar to previous studies reporting on imaging related to genital sensitivity.

BACKGROUND: Bilateral acute subdural hematomas (aSDHs) present a significant challenge for neurosurgeons, particularly due to the risk of contralateral hematoma enlargement following unilateral evacuation and subsequent volume shifts. This complexity is further compounded in elderly patients with preexisting health conditions. OBSERVATIONS: This case report presents a novel minimally invasive approach for managing bilateral aSDHs in a 76-year-old female. The patient developed bilateral aSDHs following head trauma and was considered high risk for general anesthesia and bilateral craniotomies. A minimally invasive technique was utilized, involving twist-drill craniostomy under local anesthesia combined with pressure-controlled fibrinolytic therapy using the IRRAflow and LiquoGuard 7 systems. The patient was treated with continuous pressure–controlled irrigation therapy using an electrolyte solution containing 200,000 IU/l of urokinase infused at a rate of 100 ml/hr. The patient showed significant improvement, with complete resolution of the hematomas and no residual neurological deficits. LESSONS: This case demonstrates the effectiveness of minimally invasive techniques that avoid the risks associated with general anesthesia and craniotomies. While these findings are promising, they should be interpreted with caution and require prospective confirmation in a larger cohort of patients. Nonetheless, they align with the recent literature that supports minimally invasive approaches for aSDHs. https://thejns.org/doi/10.3171/CASE24577

Background: Transforaminal lumbar interbody fusion (TLIF) is one of the most frequently performed spinal fusion techniques, and this minimally invasive (MIS) approach has advantages over the traditional open approach. A drawback is the higher radiation exposure for the surgeon when conventional fluoroscopy (2D-fluoroscopy) is used. While computer-assisted navigation (CAN) reduce the surgeon’s radiation exposure, the patient’s exposure is higher. When we investigated 2D-fluoroscopically guided and 3D-navigated MIS TLIF in a randomized controlled trial, we detected low radiation doses for both the surgeon and the patient in the 2D-fluoroscopy group. Therefore, we extended the dataset, and herein, we report the radiation-sparing surgical technique of 2D-fluoroscopy-guided MIS TLIF. Methods: Monosegmental and bisegmental MIS TLIF was performed on 24 patients in adherence to advanced radiation protection principles and a radiation-sparing surgical protocol. Dedicated dosemeters recorded patient and surgeon radiation exposure. For safety assessment, pedicle screw accuracy was graded according to the Gertzbein–Robbins classification. Results: In total, 99 of 102 (97.1%) pedicle screws were correctly positioned (Gertzbein grade A/B). No breach caused neurological symptoms or necessitated revision surgery. The effective radiation dose to the surgeon was 41 ± 12 µSv per segment. Fluoroscopy time was 64 ± 34 s and 75 ± 43 radiographic images per segment were performed. Patient radiation doses at the neck, chest, and umbilical area were 65 ± 40, 123 ± 116, and 823 ± 862 µSv per segment, respectively. Conclusions: Using a dedicated radiation-sparing free-hand technique, 2D-fluoroscopy-guided MIS TLIF is successfully achievable with low radiation exposure to both the surgeon and the patient. With this technique, the maximum annual radiation exposure to the surgeon will not be exceeded, even with workday use.