Rafal Chojak

Background: Glioblastoma (GBM) adapts to therapy through coordinated malignant-cell and microenvironmental responses, but the mechanisms linking treatment-associated inflammation to tumor-cell phenotypic plasticity remain poorly defined. Here, we investigated whether preoperative temozolomide exposure is associated with inflammatory-repair remodeling and a ROCK-linked therapeutic vulnerability in recurrent GBM using a window-of-opportunity clinical trial cohort. Methods: We integrated patient-resolved single-cell transcriptomics, spatial RNA profiling and multiplex protein imaging with experimental perturbations and orthotopic glioblastoma models. In the presurgical window-of-opportunity subgroup of NCT05236036 , four patients with recurrent glioblastoma received additional preoperative temozolomide (TMZ; 150 mg/m2/day for 5 days) before resection and were compared with three recurrent comparators who did not receive additional preoperative TMZ. Results: Across seven tumors, malignant-cell inflammatory activity covaried with integrin-binding and wound-healing programs (median partial ρ = 0.45 and 0.42, respectively). Tumors exposed to preoperative TMZ showed enrichment of inflammatory, chemokine, adhesion and wound-healing programs (GSEA q < 0.05), with the direction of enrichment preserved in all leave-one-patient-out analyses. In two tumors exposed to preoperative TMZ, CXCL12 localized to vascular territories, whereas chemokine and wound-repair programs increased near injury-reference regions. Across seven specimens analyzed by multiplex protein imaging, MYL9 abundance correlated with local CXCL12 (ρ = 0.61), phosphorylated MYPT1 (ρ = 0.48) and nuclear phosphorylated STAT3 (ρ = 0.45), with positive associations in every specimen. Experimentally, TMZ increased CXCL8 and reactive-state markers and enhanced subsequent scratch closure, while CXCL8 and CXCL12 increased MLC2 phosphorylation. Fasudil attenuated TNF-NF-κB, inflammatory-response and IFN-γ-response programs in TMZ-treated cells and reduced scratch closure and p-MLC2 in complementary assays. Across three orthotopic models, fasudil plus TMZ prolonged survival versus TMZ alone (model-stratified HR, 0.21; 95% CI, 0.07-0.61; P = 0.001). Conclusions: These findings link treatment-associated inflammatory-repair programs with cytoskeletal remodeling and support further translational evaluation of fasudil plus TMZ in glioblastoma.

Purpose: Spatial patterns of glioblastoma (GBM) progression inform focal salvage eligibility, but interpretation across studies is limited by heterogeneous spatial definitions, high between-study heterogeneity, and incomplete reporting of non-enhancing/FLAIR-dominant progression. We synthesized reported progression-location involvement after upfront radiotherapy/temozolomide (RT/TMZ) and salvage therapy. Methods: We systematically searched PubMed and Scopus from January 1, 2000, to February 1, 2026, and performed arm-level random-effects meta-analysis of logit-transformed proportions. Enhancing progression was harmonized as non-mutually exclusive local/in-field, marginal/field-edge, and distant/out-of-field involvement among evaluable cases, using each study’s spatial framework. The supplementary broad escape-pattern construct was defined as reported progression beyond purely local/in-field enhancing failure. Results: We included 107 studies (122 arms; 10,529 patients). At first progression after upfront RT/TMZ ± TTF, reported local/in-field enhancing involvement among evaluable cases was 79.2% (95% CI 75.7–82.3; k = 94; n = 6,989; I²=84.8%), and distant/out-of-field involvement was 16.9% (95% CI 14.3–19.9; k = 89; n = 6,493; I²=85.2%). After salvage therapy, local/in-field involvement remained the majority pattern reported among evaluable cases (59.8%, 95% CI 52.8–66.4; k = 27; n = 1,572; I²=80.5%), with distant/out-of-field involvement of 17.5% (95% CI 12.9–23.3; k = 21; n = 1,307; I²=75.5%) and a supplementary broad escape-pattern estimate of 38.6% (95% CI 31.9–45.9; k = 27; n = 1,572; I²=80.1%). Non-enhancing/FLAIR-dominant progression was sparsely and likely selectively reported; only six recurrent/salvage arms contributed data, yielding an exploratory pooled estimate of 27.8% (95% CI 12.8–50.3; n = 216; I²=75.7%). Conclusion: Published GBM cohorts show predominantly local/in-field enhancing progression after upfront therapy (~ 80%) and persistent majority local/in-field involvement after salvage therapy (~ 60%). Standardized reporting of enhancing, non-enhancing/FLAIR-dominant, disseminated, posterior fossa, and brainstem progression is needed.

Undifferentiated pleomorphic sarcoma (UPS) is a rare and aggressive soft tissue tumor of unknown histogenesis. UPS most often arises in the extremities or trunk, where wide surgical excision is feasible. Rarely, UPS involves the intracranial space, where critical structures may inhibit complete resection. Given its rarity and historical misclassification as malignant fibrous histiocytoma (MFH), knowledge of intracranial UPS is limited, and there are no clear treatment guidelines. We systematically reviewed all available cases of intracranial UPS to consolidate existing literature and assess prognosis and management considerations. A systematic review was conducted according to PRISMA guidelines. PubMed and Embase were searched for reports of intracranial UPS or storiform-pleomorphic MFH. Eligible studies included at least one histologically confirmed case treated with surgery, chemotherapy, or radiotherapy and reported outcomes. Data on demographics, tumor location, treatment, follow-up, and survival were extracted. Event-free survival (EFS) and overall survival (OS) were analyzed by treatment modality, age, sex, and tumor location using Kaplan-Meier and log-rank tests. From 801 records, 40 studies with 48 patients were included. The median age was 45 years, and 50% were female. 15% had prior radiotherapy. Most tumors were extra-axial (45%) and nearly all patients underwent surgery, with 82.1% achieving gross total resection. Median EFS and OS were 18 and 24 months, respectively. No survival differences were seen by treatment modality, age, or sex. Overall survival was longer for extra-axial tumors compared to intra-axial or skull base tumors ( p = 0.016). Intracranial UPS is a rare and aggressive tumor, with worse prognosis compared to those that are extracranial. Among factors that we evaluated, extra-axial location was the strongest positive prognostic factor. Surgical resection with adjuvant chemoradiation showed the longest median survival. Ongoing case reports are required to refine management guidelines and improve patient outcomes.

Diseases of the central nervous system (CNS) manifest through a complex, dynamic network of intercellular communication. Glioblastoma (GBM), the most common and aggressive primary brain tumor, is emblematic of this complexity, with its rapid progression and dismal prognosis measured in months rather than years. GBM's biology is driven by intricate signaling molecule exchanges between neoplastic and stromal cells, underpinning aggressive disease progression. Here, we describe a detailed cerebral open-flow microperfusion (cOFM) protocol in GBM mouse models, enabling real-time longitudinal monitoring of tumor microenvironment dynamics within the interstitial fluid (ISF). Our approach describes the implantation of durable guide cannula head-mounts, their use for intracerebral glioma engraftment directly through the guide, and the collection of high-fidelity cOFM samples for metabolomic and proteomic LC-MS analyses. Crucially, cOFM overcomes the molecular size limitations of traditional microdialysis. Beyond GBM, cOFM methodology promises transformative insights into a spectrum of CNS disorders, including neurodegenerative, epileptic, and neuropsychiatric conditions, through its capacity to provide etiological and treatment-responsive biomarkers within their respective animal models.

Diseases of the central nervous system (CNS) manifest through a complex, dynamic network of intercellular communication. Glioblastoma (GBM), the most common and aggressive primary brain tumor, is emblematic of this complexity, with its rapid progression and dismal prognosis measured in months rather than years. GBM's biology is driven by intricate signaling molecule exchanges between neoplastic and stromal cells, underpinning aggressive disease progression. Here, we describe a detailed cerebral open-flow microperfusion (cOFM) protocol in GBM mouse models, enabling real-time longitudinal monitoring of tumor microenvironment dynamics within the interstitial fluid (ISF). Our approach describes the implantation of durable guide cannula head-mounts, their use for intracerebral glioma engraftment directly through the guide, and the collection of high-fidelity cOFM samples for metabolomic and proteomic LC-MS analyses. Crucially, cOFM overcomes the molecular size limitations of traditional microdialysis. Beyond GBM, cOFM methodology promises transformative insights into a spectrum of CNS disorders, including neurodegenerative, epileptic, and neuropsychiatric conditions, through its capacity to provide etiological and treatment-responsive biomarkers within their respective animal models.

Gliomas represent a heterogeneous group of primary brain tumors with variable biological behavior. High-grade variants, notably glioblastomas, exhibit aggressive growth and a poor prognosis. Although surgical resection is central to management, it may lead to systemic and regional postoperative complications that adversely affect outcomes. While neurological complications have been extensively studied, comprehensive analyses of non-neurological sequelae remain limited. This study aimed to estimate the pooled proportion of postoperative systemic and regional complications following glioma resection and to identify factors influencing these proportions. A systematic review and meta-analysis was conducted per PRISMA guidelines. PubMed, Web of Science, and Embase were searched for English-language articles published between January 2000 and November 2024 reporting postoperative complications in glioma resection patients. Pooled proportion were calculated using a random-effects model, and meta-regression assessed the impact of covariates including patient age, gender, publication date, geographical location, and sample size. Seventy-seven studies were included. The pooled proportions for postoperative complications were as follows: venous thromboembolism, 4.92% (95% CI: 1.51–10.05%); deep vein thrombosis, 4.75% (95% CI: 2.86–7.05%); urinary tract infection, 3.77% (95% CI: 0.81–8.47%); hydrocephalus, 2.53% (95% CI: 1.37–3.97%); pulmonary infection, 2.39% (95% CI: 1.15–3.99%); cerebrospinal fluid leak, 2.22% (95% CI: 0.99–3.87%); surgical site infection, 2.21% (95% CI: 1.48–3.07%); meningitis, 1.49% (95% CI: 0.47–2.96%); pulmonary embolism, 1.33% (95% CI: 0.74–2.06%); and sepsis, 1.12% (95% CI: 0.08–3.02%). Significant heterogeneity was observed across studies, with meta-regression revealing that geographical location, publication date, and patient age were significant moderators influencing certain complication rates. This meta-analysis demonstrates that, while systemic and regional complication rates following glioma resection are relatively low, they remain clinically significant. In particular, venous thromboembolism and deep vein thrombosis are notably prevalent. Moreover, significant heterogeneity—shaped by geography, publication date, and patient age—underscores the need for tailored perioperative strategies and further research.

Meningitis is a potential complication of elective intracranial surgery (EIS). The prevalence of meningitis after EIS varies greatly in the literature. The objective of this study was to estimate the overall pooled prevalence of meningitis following EIS. Four databases (PubMed, Scopus, Web of Science, and Embase) were searched to identify relevant studies. Meta-analyses of proportions were used to combine data. Cochran's Q and I² statistics were used to assess and quantify heterogeneity. Additionally, several subgroup analyses were conducted to investigate the source of heterogeneity and examine differences in the prevalence based on variables such as geographical regions, income level, and meningitis type. The meta-analysis included 83 studies (30 959 patients) from 26 countries. The overall pooled prevalence of meningitis after EIS was 1.6% (95% CI 1.1–2.1), with high heterogeneity present (I² = 88%). The pooled prevalence in low- to middle-income countries and high-income countries was 2.7% (95% CI 1.6–4.1) and 1.2% (95% CI 0.8–1.7), respectively. Studies that reported only aseptic meningitis had a pooled prevalence of 3.2% (95% CI 1.3–5.8). The pooled prevalence was 2.8% (95% CI 1.5–4.5) in studies that reported only bacterial meningitis. Similar prevalence rates of meningitis were observed in the subgroups of tumor resection, microvascular decompression, and aneurysm clipping. Meningitis is a rare but not exceptional complication following EIS, with an estimated prevalence of 1.6%.

Purpose: Despite the improvement in treatment and prognosis of primary central nervous system lymphoma (PCNSL) over the last decades, the 5-year survival rate is approximately 30%; thus, new therapeutic approaches are needed to improve patient survival. The study’s aim was to evaluate the role of surgical resection of PCNSL. Methods: Primary outcomes were the overall survival (OS) and progression-free survival (PFS) of patients with PCNSL who underwent surgical resection versus biopsy alone. The meta-analysis was conducted to calculate pooled hazard ratios (HRs) under a random-effects model for the time-to-event variables. The odds ratios (ORs) were calculated for binary, secondary outcome parameters. Results: Seven studies (n = 1046) were included. We found that surgical resection was associated with significantly better OS (HR 0.63 [95% CI 0.51–0.77]) when compared with biopsy. PFS was also significantly improved (HR 0.64 [95% CI 0.49–0.85]) in patients who underwent resection compared with those who underwent biopsy. The heterogeneity for OS and PFS was low (I2 = 7% and 24%, respectively). We also found that patients who underwent biopsy more often had multiple (OR 0.38 [95% CI 0.19–0.79]) or deep-seated (OR 0.20 [95% CI 0.12–0.34]) lesions compared with those who underwent surgical resection. There were no significant differences in chemotherapy or radiotherapy use or the occurrence of postoperative complications between the two groups. Conclusion: In selected patients, surgical resection of PCNSL is associated with significantly better overall survival and progression-free survival compared with biopsy alone.

Background: Most traumatic brain injuries (TBIs) are mild (GCS score of 13–15). Patients with mild TBI (mTBI) are generally in good condition. In some cases, a neurological deterioration (manifested by a drop of ≥1 point in GCS score) can occur and neurosurgical intervention (NI) may be needed. Because of that, these patients are frequently admitted to a hospital for observation. The aim of our study was to determine the number of patients with mTBI that deteriorate or need NI. We also considered an economic aspect of hospital admissions of these patients.Methods: The study group consisted of 186 adult patients admitted to the neurosurgical department due to mTBI. Patients were divided into three groups according to an initial GCS score. The occurrence of deterioration, need for NI, length of stay (LOS), cost of stay and occurrence of death were analyzed.Results: The deterioration was observed in 7 (3.76%) out of all cases. In 3 (1.61%) of them, the NI was needed. The average LOS was 7.96 days and it was closely linked with an initial GCS score (p < 0.001). The total cost of stay of all patients included in this study was about 1,188,668 PLN (306,357 USD).Conclusion: The deterioration occurred in a small number of patients with mTBI, the need for NI was even less common. Hospitalization of these patients is expensive. Further studies with prognostic model helping decide on admission/discharge are necessary.