D-Loop Mutations as Prognostic Markers in Glioblastoma-A Pilot Study.

Glioblastoma, a highly aggressive brain tumor, poses significant treatment challenges. A deeper investigation into its molecular complexity is essential for the identification of novel prognostic biomarkers and therapeutic strategies, potentially improving patient outcomes in terms of survival and quality of life. While nuclear DNA mutations have been extensively studied, the role of mitochondrial DNA (mtDNA) mutations, specifically in the D-loop region, remains poorly understood. This prospective case-control study aimed to assess the prognostic significance of the mtDNA D-loop m.16126T>C variant in glioblastoma patients. Immunohistochemistry and droplet digital PCR (ddPCR) were employed for mutation analysis, complemented by statistical analyses and a literature review. The study cohort comprised 22 glioblastoma patients (mean age 59.36 ± 14.17, 12 (54.55%) females), and 25 controls (59.48 ± 13.22, 12 (80%) females). The D-loop m.16126T>C variant was observed in four (18%) of the glioblastoma samples and was associated with shorter median survival (9.5 vs. 18 months; p = 0.016, log-rank test). This study underscores the importance of investigating mtDNA, especially D-loop variants, in glioblastoma, suggesting its potential as a prognostic biomarker and, therefore, its possible therapeutic targets, warranting further exploration.

Predictors of 30-Day Mortality for Surgically Treated Patients with Spontaneous Supratentorial Intracerebral Hemorrhage and Validation of the Surgical Swedish Intracerebral Hemorrhage Score: A Retrospective Single-Center Analysis of 136 Cases.

OBJECTIVE: We aimed to identify independent risk factors of 30-day mortality in patients with surgically treated spontaneous supratentorial intracerebral hemorrhage (ICH), validate the Surgical Swedish ICH (SwICH) score within Polish healthcare system, and compare the SwICH score to the ICH score. METHODS: We carried out a single-center retrospective analysis of the medical data juxtaposed with computed tomography scans of 136 ICH patients treated surgically between 2008 and 2022. Statistical analysis was performed using the same characteristics as in the SwICH score and the ICH score. Backward stepwise logistic regression with both 5-fold crossvalidation and 1000× bootstrap procedure was used to create new scoring system. Finally predictive potential of these scales were compared. RESULTS: The most important predictors of 30-day mortality were: ICH volume (P < 0.01), Glasgow Coma Scale at admission (P < 0.01), anticoagulant status (P = 0.03), and age (P < 0.01). The SwICH score appears to have a better predictive potential than the ICH score, although this did not reach statistical significance [area under the curve {AUC}: 0.789 (95% confidence interval {CI}: 0.715-0.863) vs. AUC: 0.757 (95% CI: 0.677-0.837)]. Moreover, based on the analyzed characteristics, we developed our score (encompassing: age, ICH volume, anticoagulants status, Glasgow Coma Scale at admission), [AUC of 0.872 (95% CI: 0.815-0.929)]. This score was significantly better than previous ones. CONCLUSIONS: Differences in health care systems seem to affect the accuracy of prognostic scales for patients with ICH, including possible differences in indications for surgery and postoperative care. Thus, it is important to validate assessment tools before they can be applied in a new setting and develop population-specific scores. This may improve the effectiveness of risk stratification in patients with ICH.

Automated volumetric evaluation of intracranial compartments and cerebrospinal fluid distribution on emergency trauma head CT scans to quantify mass effect.

Background: Intracranial space is divided into three compartments by the falx cerebri and tentorium cerebelli. We assessed whether cerebrospinal fluid (CSF) distribution evaluated by a specifically developed deep-learning neural network (DLNN) could assist in quantifying mass effect. Methods: Head trauma CT scans from a high-volume emergency department between 2018 and 2020 were retrospectively analyzed. Manual segmentations of intracranial compartments and CSF served as the ground truth to develop a DLNN model to automate the segmentation process. Dice Similarity Coefficient (DSC) was used to evaluate the segmentation performance. Supratentorial CSF Ratio was calculated by dividing the volume of CSF on the side with reduced CSF reserve by the volume of CSF on the opposite side. Results: Two hundred and seventy-four patients (mean age, 61 years ± 18.6) after traumatic brain injury (TBI) who had an emergency head CT scan were included. The average DSC for training and validation datasets were respectively: 0.782 and 0.765. Lower DSC were observed in the segmentation of CSF, respectively 0.589, 0.615, and 0.572 for the right supratentorial, left supratentorial, and infratentorial CSF regions in the training dataset, and slightly lower values in the validation dataset, respectively 0.567, 0.574, and 0.556. Twenty-two patients (8%) had midline shift exceeding 5 mm, and 24 (8.8%) presented with high/mixed density lesion exceeding >25 ml. Fifty-five patients (20.1%) exhibited mass effect requiring neurosurgical treatment. They had lower supratentorial CSF volume and lower Supratentorial CSF Ratio (both p < 0.001). A Supratentorial CSF Ratio below 60% had a sensitivity of 74.5% and specificity of 87.7% (AUC 0.88, 95%CI 0.82-0.94) in identifying patients that require neurosurgical treatment for mass effect. On the other hand, patients with CSF constituting 10-20% of the intracranial space, with 80-90% of CSF specifically in the supratentorial compartment, and whose Supratentorial CSF Ratio exceeded 80% had minimal risk. Conclusion: CSF distribution may be presented as quantifiable ratios that help to predict surgery in patients after TBI. Automated segmentation of intracranial compartments using the DLNN model demonstrates a potential of artificial intelligence in quantifying mass effect. Further validation of the described method is necessary to confirm its efficacy in triaging patients and identifying those who require neurosurgical treatment.

The Anterior Inferior Cerebral Artery Variability in the Context of Neurovascular Compression Syndromes: A Narrative Review.

The anterior inferior cerebellar artery (AICA) is situated within the posterior cranial fossa and typically arises from the basilar artery, usually at the pontomedullary junction. AICA is implicated in various clinical conditions, encompassing the development of aneurysms, thrombus formation, and the manifestation of lateral pontine syndrome. Furthermore, owing to its close proximity to cranial nerves within the middle cerebellopontine angle, AICA's pulsatile compression at the root entry/exit zone of cranial nerves may give rise to specific neurovascular compression syndromes (NVCs), including hemifacial spasm (HFS) and geniculate neuralgia concurrent with HFS. In this narrative review, we undertake an examination of the influence of anatomical variations in AICA on the occurrence of NVCs. Significant methodological disparities between cadaveric and radiological studies (CTA, MRA, and DSA) were found, particularly in diagnosing AICA's absence, which was more common in radiological studies (up to 36.1%) compared to cadaver studies (less than 5%). Other observed variations included atypical origins from the vertebral artery and basilar-vertebral junction, as well as the AICA-and-PICA common trunk. Single cases of arterial triplication or fenestration have also been documented. Specifically, in relation to HFS, AICA variants that compress the facial nerve at its root entry/exit zone include parabola-shaped loops, dominant segments proximal to the REZ, and anchor-shaped bifurcations impacting the nerve's cisternal portion.

European survey on neurosurgical management of primary central nervous system lymphomas and preoperative corticosteroid therapy.

Introduction: Preoperative corticosteroid therapy (CST) is common in primary central nervous system lymphoma (PCNSL) and may complicate histopathological diagnosis. There is an ongoing debate on the best management after preoperative CST. Research question: We aimed to survey how different European neurosurgical units treat PCNSL patients after preoperative CST. Methods: An English-language survey consisting of 21 questions addressing the management of patients with suspected PCNSL and preoperative CST was sent to European hospitals. The survey also included three clinical cases to assess the decision-making process in a clinical setting. Results: The survey was completed by 74 European hospitals. There was no clear consensus on how to treat a patient with PCNSL after CST. Accordingly, 24.3% responded that they would generally defer surgery regardless of a possible radiological response, 47.3% would defer surgery only if there is regression in preoperative MRI and the remaining 28.4% would defer surgery only if the tumor had completely vanished. Furthermore, there were distinct discrepancies in responses of neurosurgical units regarding their general management approach and their case-based decision in the three example cases. The results of our survey also showed regional differences and differences in treatment decisions between high-, intermediate- and low-volume centers. Discussion and conclusion: There was no clear consensus on how to treat patients with suspected PCNSL and preoperative CST. Furthermore, most centers also showed inconsistencies in their responses regarding their general approach as well as individual patient treatment. More high-quality evidence-based recommendations are needed to improve consensus and thus patient care.

Autophagy Inhibition with Chloroquine Increased Pro-Apoptotic Potential of New Aziridine-Hydrazide Hydrazone Derivatives against Glioblastoma Cells.

Tumor therapy escape due to undesired side effects induced by treatment, such as prosurvival autophagy or cellular senescence, is one of the key mechanisms of resistance that eventually leads to tumor dormancy and recurrence. Glioblastoma is the most frequent and practically incurable neoplasm of the central nervous system; thus, new treatment modalities have been investigated to find a solution more effective than the currently applied standards based on temozolomide. The present study examined the newly synthesized compounds of aziridine-hydrazide hydrazone derivatives to determine their antineoplastic potential against glioblastoma cells in vitro. Although the output of our investigation clearly demonstrates their proapoptotic activity, the cytotoxic effect appeared to be blocked by treatment-induced autophagy, the phenomenon also detected in the case of temozolomide action. The addition of an autophagy inhibitor, chloroquine, resulted in a significant increase in apoptosis triggered by the tested compounds, as well as temozolomide. The new aziridine-hydrazide hydrazone derivatives, which present cytotoxic potential against glioblastoma cells comparable to or even higher than that of temozolomide, show promising results and, thus, should be further investigated as antineoplastic agents. Moreover, our findings suggest that the combination of an apoptosis inducer with an autophagy inhibitor could optimize chemotherapeutic efficiency, and the addition of an autophagy inhibitor should be considered as an optional adjunctive therapy minimizing the risk of tumor escape from treatment.

The Superior Cerebellar Artery: Variability and Clinical Significance.

The superior cerebellar artery (SCA) arises from the distal part of the basilar artery and passes by the oculomotor, trochlear, and trigeminal nerves. SCA is known to play a crucial role in the development of trigeminal neuralgia. However, due to its anatomical variability, it may also trigger other neurovascular compression (NVC), including hemifacial spasm, oculomotor nerve palsy, and ocular neuromyotonia. Additionally, it may be associated with ischemic syndromes and aneurysm development, highlighting its clinical significance. The most common anatomical variations of the SCA include duplication, a single vessel origin from the posterior cerebral artery (PCA), and a common trunk with PCA. Rarely observed variants include bifurcation and origin from the internal carotid artery. Certain anatomical variants such as early bifurcation and caudal course of duplicated SCA trunk may increase the risk of NVC. In this narrative review, we aimed to examine the impact of the anatomical variations of SCA on the NVCs based on papers published in Pubmed, Scopus, and Web of Science databases with a snowballing approach. Our review emphasizes the importance of a thorough understanding of the anatomical variability of SCA to optimize the management of patients with NVCs associated with this artery.

The Underlying Pathogenesis of Neurovascular Compression Syndromes: A Systematic Review.

Neurovascular compression syndromes (NVC) are challenging disorders resulting from the compression of cranial nerves at the root entry/exit zone. Clinically, we can distinguish the following NVC conditions: trigeminal neuralgia, hemifacial spasm, and glossopharyngeal neuralgia. Also, rare cases of geniculate neuralgia and superior laryngeal neuralgia are reported. Other syndromes, e.g., disabling positional vertigo, arterial hypertension in the course of NVC at the CN IX-X REZ and torticollis, have insufficient clinical evidence for microvascular decompression. The exact pathomechanism leading to characteristic NVC-related symptoms remains unclear. Proposed etiologies have limited explanatory scope. Therefore, we have examined the underlying pathomechanisms stated in the medical literature. To achieve our goal, we systematically reviewed original English language papers available in Pubmed and Web of Science databases before 2 October 2021. We obtained 1694 papers after eliminating duplicates. Only 357 original papers potentially pertaining to the pathogenesis of NVC were enrolled in full-text assessment for eligibility. Of these, 63 were included in the final analysis. The systematic review suggests that the anatomical and/or hemodynamical changes described are insufficient to account for NVC-related symptoms by themselves. They must coexist with additional changes such as factors associated with the affected nerve (e.g., demyelination, REZ modeling, vasculature pathology), nucleus hyperexcitability, white and/or gray matter changes in the brain, or disturbances in ion channels. Moreover, the effects of inflammatory background, altered proteome, and biochemical parameters on symptomatic NVC cannot be ignored. Further studies are needed to gain better insight into NVC pathophysiology.

If Artificial In Vitro Microenvironment Can Influence Tumor Drug Resistance Network via Modulation of lncRNA Expression?-Comparative Analysis of Glioblastoma-Derived Cell Culture Models and Initial Tumors In Vivo.

The tumor resistance of glioblastoma cells in vivo is thought to be enhanced by their heterogeneity and plasticity, which are extremely difficult to curb in vitro. The external microenvironment shapes the molecular profile of tumor culture models, thus influencing potential therapy response. Our study examines the expression profile of selected lncRNAs involved in tumor resistance network in three different glioblastoma-derived models commonly utilized for testing drug response in vitro. Differential expression analysis revealed significant divergence in lncRNA profile between parental tumors and tumor-derived cell cultures in vitro, including the following particles: MALAT1, CASC2, H19, TUSC7, XIST, RP11-838N2.4, DLX6-AS1, GLIDR, MIR210HG, SOX2-OT. The examined lncRNAs influence the phenomenon of tumor resistance via their downstream target genes through a variety of processes: multi-drug resistance, epithelial-mesenchymal transition, autophagy, cell proliferation and viability, and DNA repair. A comparison of in vivo and in vitro expression identified differences in the levels of potential lncRNA targets, with the highest discrepancies detected for the MDR1, LRP1, BCRP and MRP1 genes. Co-expression analyses confirmed the following interrelations: MALAT1-TYMS, MALAT1-MRP5, H19-ZEB1, CASC2-VIM, CASC2-N-CAD; they additionally suggest the possibility of MALAT1-BCRP, MALAT1-mTOR and TUSC7-PTEN interconnections in glioblastoma. Although our results clearly demonstrate that the artificial ex vivo microenvironment changes the profile of lncRNAs related to tumor resistance, it is difficult to anticipate the final phenotypic effect, since this phenomenon is a complex one that involves a network of molecular interactions underlying a variety of cellular processes.

Risk Factors for Recanalization after Coil Embolization.

The aim of our study was to identify risk factors for recanalization 6 months after coil embolization using clinical data followed by computational fluid dynamics (CFD) analysis. METHODS: Firstly, clinical data of 184 patients treated with coil embolization were analyzed retrospectively. Secondly, aneurysm models for high/low recanalization risk were generated based on ROC curves and their cut-off points. Afterward, CFD was utilized to validate the results. RESULTS: In multivariable analysis, aneurysm filling during the first embolization was an independent risk factor whilst packing density was a protective factor of recanalization after 6 months in patients with aSAH. For patients with unruptured aneurysms, packing density was found to be a protective factor whilst the aneurysm neck size was an independent risk factor. Complex flow pattern and multiple vortices were associated with aneurysm shape and were characteristic of the high recanalization risk group. CONCLUSIONS: Statistical analysis suggested that there are various factors influencing recanalization risk. Once certain values of morphometric parameters are exceeded, a complex flow with numerous vortices occurs. This phenomenon was revealed due to CFD investigations that validated our statistical research. Thus, the complex flow pattern itself can be treated as a relevant recanalization predictor.

Porous Media Computational Fluid Dynamics and the Role of the First Coil in the Embolization of Ruptured Intracranial Aneurysms.

BACKGROUND: The objective of our project was to identify a late recanalization predictor in ruptured intracranial aneurysms treated with coil embolization. This goal was achieved by means of a statistical analysis followed by a computational fluid dynamics (CFD) with porous media modelling approach. Porous media CFD simulated the hemodynamics within the aneurysmal dome after coiling. METHODS: Firstly, a retrospective single center analysis of 66 aneurysmal subarachnoid hemorrhage patients was conducted. The authors assessed morphometric parameters, packing density, first coil volume packing density (1st VPD) and recanalization rate on digital subtraction angiograms (DSA). The effectiveness of initial endovascular treatment was visually determined using the modified Raymond-Roy classification directly after the embolization and in a 6- and 12-month follow-up DSA. In the next step, a comparison between porous media CFD analyses and our statistical results was performed. A geometry used during numerical simulations based on a patient-specific anatomy, where the aneurysm dome was modelled as a separate, porous domain. To evaluate hemodynamic changes, CFD was utilized for a control case (without any porosity) and for a wide range of porosities that resembled 1-30% of VPD. Numerical analyses were performed in Ansys CFX solver. RESULTS: A multivariate analysis showed that 1st VPD affected the late recanalization rate (p < 0.001). Its value was significantly greater in all patients without recanalization (p < 0.001). Receiver operating characteristic curves governed by the univariate analysis showed that the model for late recanalization prediction based on 1st VPD (AUC 0.94 (95%CI: 0.86-1.00) is the most important predictor of late recanalization (p < 0.001). A cut-off point of 10.56% (sensitivity-0.722; specificity-0.979) was confirmed as optimal in a computational fluid dynamics analysis. The CFD results indicate that pressure at the aneurysm wall and residual flow volume (blood volume with mean fluid velocity > 0.01 m/s) within the aneurysmal dome tended to asymptotically decrease when VPD exceeded 10%. CONCLUSIONS: High 1st VPD decreases the late recanalization rate in ruptured intracranial aneurysms treated with coil embolization (according to our statistical results > 10.56%). We present an easy intraoperatively calculable predictor which has the potential to be used in clinical practice as a tip to improve clinical outcomes.

Frameless x-ray-based lead re-implantation after partial hardware removal of deep brain stimulation system with preservation of intracerebral trajectories.

BACKGROUND: Deep brain stimulation (DBS) is an established treatment for patients with medical refractory movement disorders with continuously increasing use also in other neurological and psychiatric diseases. Early and late complications can lead to revision surgeries with partial or complete DBS-system removal. In this study, we aimed to report on our experience with a frameless x-ray-based lead re-implantation technique after partial hardware removal or dysfunction of DBS-system, allowing the preservation of intracerebral trajectories. METHODS: We describe a surgical procedure with complete implant removal due to infection except for the intracranial part of the electrode and with non-stereotactic electrode re-implantation. A retrospective analysis of a patient series treated using this technique was performed and the surgical outcome was evaluated including radiological and clinical parameters. RESULTS: A total of 8 DBS-patients with lead re-implantation using the frameless x-ray-based method were enrolled in the study. A revision of 14 leads was performed, whereof a successful lead re-implantation could be achieved without any problems in 10 leads (71%). In two patients (one patient with dystonia and one patient with tremor), the procedure was not successful, so we placed both leads frame-based stereotactically. CONCLUSIONS: The described x-ray-based technique allows a reliable frameless electrode re-implantation after infection and electrode dysfunction and might represent an efficient alternative to frame-based procedures for lead revision making the preservation of intracerebral trajectories possible.

The Role of Urine F2-ISOPROSTANE CONcentration in Delayed Cerebral Ischemia after Aneurysmal Subarachnoid Haemorrhage-A Poor Prognostic Factor.

Background: The pathophysiology of delayed cerebral ischemia (DCI) remains unclear. One of the hypotheses suggests that reactive oxygen species play a role in its onset. Thus, we studied F2-isoprostanes (F2-IsoPs)-oxidative stress biomarkers. Our goal was to improve the early diagnosis of DCI in a non-invasive way. Methods: We conducted a prospective single center analysis of 38 aneurysmal subarachnoid hemorrhage patients. We assessed urine F2-IsoP concentration using immunoenzymatic arrays between the first and fifth day after bleeding. A correlation between urine F2-IsoP concentration and DCI occurrence was examined regarding clinical conditions and outcomes. Results: The urine F2-IsoP concentrations were greater than those in the control groups (p < 0.001). The 3rd day urine F2-IsoPs concentrations were correlated with DCI occurrence (p < 0.001) and long term outcomes after 12 months (p < 0.001). Conclusions: High levels of urine F2-IsoPs on day 3 can herald DCI.

Predicting Outcome and Conservative Treatment Failure in Patients with Skull Fracture after Traumatic Brain Injury: A Retrospective Cohort Study.

OBJECTIVE: Traumatic brain injury (TBI) remains a major cause of morbidity and mortality worldwide. The prognostic value of skull fracture (SF) remains to be clearly defined. To evaluate the need for neurosurgical intervention and determine the risk factors of conservative treatment failure (CTF), we retrieved from the hospital database the records of patients with SF after TBI. METHODS: We analyzed 146 consecutive patients (mean age: 49.8 ± 17.5 years) treated at the department of neurosurgery in a 5-year period. Clinical data, radiologic reports, and laboratory results were evaluated retrospectively. RESULTS: A total of 63% of patients were treated conservatively, 21.9% were operated on immediately, and 15.1% experienced CTF. Overall, 73.3% had a favorable outcome; the mortality rate was 13%. Intracranial bleeding occurred in 96.6% of cases, basilar SF in 61%, and cerebrospinal fluid (CSF) leak in 2.8%. The independent risk factors for outcome were Glasgow Coma Scale (GCS) score, age, and platelet count (PCT). The independent risk factors for CTF were epidural hematoma, subdural hematoma, mass effect, edema, international normalized ratio, PCT, mean platelet volume, and CSF leakage. The consensus decision tree algorithm used at the accident and emergency department indicated patients with no need for neurosurgical intervention with an accuracy of 91.7%, sensitivity of 88.9%, and featured the importance of mass effect, GCS, and epidural hematoma. CONCLUSIONS: Tests included in the complete blood count appeared useful for predicting the course in patients with SF, although the most important factors were age and neurologic status, as well as radiologic findings. Our decision tree requires further validation before it can be used in everyday practice.

Predictors for ophthalmic segment aneurysms recanalization after coiling and flow diverter embolization in 6- and 12-month follow-up.

Carotid-ophthalmic aneurysms are indication for endovascular treatment. Coil embolization is associated with a high recanalization rate and thus usage of flow diverter (FD) could constitute the treatment of choice. Although implementation of FD is very effective, it carries a significant risk of complications. The goal of our study was to find a radiological recanalization marker in order to facilitate decision process which would result in fewer treatment-related complications and in this way, to personalize endovascular therapy. We made a retrospective analysis of seventy-five patients with saccular carotid-ophthalmic aneurysms treated endovascularly. Morphometric measurements were performed in CTA 3D aneurysm models. The aneurysm size and volume were measured on the base of digital subtraction angiography (DSA) images. The treatment effectiveness was determined visually using the modified Raymond Roy classification after embolization and on the 6- and 12-month follow-up DSA. Statistica 13.1 software was used. Multivariate analyses showed that the aneurysm neck size (OR 2.51; 95%CI: 1.20-5.26), aspect ratio (OR 2.60; 95%CI: 1.27-5.21) and neck to parent artery ratio (OR 2.68; 95%CI: 1.26-5.70) were risk factors for carotid-ophthalmic aneurysms recanalization after 6 months. Of those factors, aneurysm neck size remained the only significant risk factor for carotid-ophthalmic aneurysms recanalization after 12 months (OR 5.23, 95%CI: 1.71-15.93). Various factors seem to influence recanalization. Preoperatively, if the above-mentioned predictors of recanalization are present, coiling is burdened with a high recanalization rate. In those cases, FD embolization should be considered.

Artificial microenvironment of in vitro glioblastoma cell cultures changes profile of miRNAs related to tumor drug resistance.

Purpose: The in vitro environment can influence not only the molecular background of glioblastoma drug-resistance and treatment efficiency, but also the mechanisms and pathways of cell death. Both crucial molecular pathways and the deregulation of miRNAs are thought to participate in tumor therapy-resistance. The aim of our study is to examine the potential influence of ex vivo conditions on the expression of miRNAs engaged in the machinery of tumor-drug resistance, since in vitro models are commonly used for testing new therapeutics. Methods: Glioblastoma-derived cells, cultured under three different sets of conditions, were used as experimental models in vitro. The expression of 84 miRNAs relevant to brain tumorigenesis was evaluated by multi-miRNA profiling for initial tumors and their corresponding cultures. Finally, the expression of selected miRNAs related to temozolomide-resistance (miR-125b, miR-130a, miR-21, miR-221, miR-222, miR-31, miR-149, miR-210, miR-181a) was assessed by real-time PCR for each tumor and neoplastic cells in cultures. Results: Our results demonstrate significant discrepancies in the expression of several miRNAs between tumor cells in vivo and in vitro, with miR-130a, miR-221, miR-31, miR-21, miR-222, miR-210 being the most marked. Also differences were observed between particular models in vitro. The results of computational analysis revealed the interplay between examined miRNAs and their targets involved in processes of glioblastoma chemosensitivity, including the genes relevant to temozolomide response (MGMT, PTEN, MDM2, TP53, BBC3A). Conclusion: The artificial environment may influence the selective proliferation of cell populations carrying specific patterns of miRNAs and/or the phenotype of neoplastic cells (eg differentiation) by the action of molecular events including miRNAs. These phenomena may influence the tumor-responsiveness to particular drugs, disturbing the evaluation of their efficacy in vitro, with unpredictable results caused by the interdependency of molecular pathways.

Mortality After Traumatic Brain Injury in Elderly Patients: A New Scoring System.

BACKGROUND: Traumatic brain injury (TBI) remains a life-threatening condition characterized by growing incidence worldwide, particularly in the aging population, in which the primary goal of treatment appears to be avoidance of chronic institutionalization. METHODS: To identify independent predictors of 30-day mortality or vegetative state in a geriatric population and calculate an intuitive scoring system, we screened 480 patients after TBI treated at a single department of neurosurgery over a 2-year period. We analyzed data of 214 consecutive patients aged ≥65 years, including demographics, medical history, cause and time of injury, neurologic state, radiologic reports, and laboratory results. A predictive model was developed using logistic regression modeling with a backward stepwise feature selection. RESULTS: The median Glasgow Coma Scale (GCS) score on admission was 14 (interquartile range, 12-15), whereas the 30-day mortality or vegetative state rate amounted to 23.4%. Starting with 20 predefined features, the final prediction model highlighted the importance of GCS motor score (odds ratio [OR], 0.17; 95% confidence interval [CI], 0.09-0.32); presence of comorbid cardiac, pulmonary, or renal dysfunction or malignancy (OR, 2.86; 9 5% CI, 1.08-7.61); platelets ≤100 × 109 cells/L (OR, 13.60; 95% CI, 3.33-55.49); and red blood cell distribution width coefficient of variation ≥14.5% (OR, 2.91; 95% CI, 1.09-7.78). The discovered coefficients were used for nomogram development. It was further simplified to facilitate clinical use. The proposed scoring system, Elderly Traumatic Brain Injury Score (eTBI Score), yielded similar performance metrics. CONCLUSIONS: The eTBI Score is the first scoring system designed specifically for older adults. It could constitute a framework for clinical decision-making and serve as an outcome predictor. Its capability to stratify risk provides reliable criteria for assessing efficacy of TBI management.

Diagnostic value of lateral ventricle ratio: a retrospective case-control study of 112 acute subdural hematomas after non-severe traumatic brain injury.

PRIMARY OBJECTIVE: To evaluate correlation between the lateral ventricle ratio (LVR) and the risk of conservative treatment failure (CTF) among patients with acute subdural hematoma (ASDH) after non-severe traumatic brain injury (TBI), we retrieved from the hospital database and performed a retrospective analysis of 1339 cases with TBI treated during the 2008-2016 period. METHODS AND PROCEDURES: 112 patients with ASDH, GCS≥ 9 and initial conservative treatment were enrolled. They were divided according to the final treatment method applied (surgical or conservative). Clinical and radiological data was evaluated. We used ROC curve analysis and multivariate logistic regression model to identify risk factors of CTF. MAIN OUTCOMES AND RESULTS: LVR higher than 1.48 calculated on admission CT scans was the strongest predictor of CTF, with sensitivity of 78.9% and specificity of 93.5% (AUC: 0.774-0.994). LVR, prolonged prothrombin time and coexisting traumatic subarachnoid hemorrhage were independent risk factors. CONCLUSIONS: Despite limitations, study results support the view that patients after non-severe TBI with ASDH and with lateral ventricle asymmetry, defined as LVR> 1.48, require surgical treatment. LVR seems to be indirect, but still the closest method to quantify intracranial compliance. Thus, in the selected group of patients without clinical symptoms of critically diminished compensatory reserve, LVR could indicate those who need a surgical decompression.

Isoprostanes as potential cerebral vasospasm biomarkers.

Despite enormous progress in medicine, symptomatic cerebral vasospasm (CVS), remains an unexplained clinical problem, which leaves both physicians and patients helpless and relying on chance, due to the lack of specific marker indicative of imminent danger as well as the lack of specific treatment. In our opinion CVS occurrence depends on dynamic disbalance between free radicals' formation (oxidative stress) and antioxidant activity. Isoprostanes are products of free-radical peroxidation of polyunsaturated fatty acids, and seem to mark a promising path for the research aiming to unravel its possible mechanism. Not only are they the biomarkers of oxidative stress in vivo and in vitro, but also have manifold biological effects (including vasoactive, inflammatory and mitogenic) via activation of the thromboxane A2 receptor (TBXA2R), both in physiological and pathophysiological processes. This review addresses the importance of isoprostanes in CVS in quest of appropriate biomarkers.

[Von Hippel-Lindau syndrome - a case report]. / Von Hippel-Lindau syndrome ­ a case report.

Von Hippel-Lindau disease (vHL, familial cerebello-retinal angiomatosis) is a rare genetic autosomal dominant disorder associated with predisposition to vascular tumors. Mutations of VHL tumor suppressor gene, located on chromosome 3p25-26, are responsible for clinical manifestation of the disease. The VHL gene product encodes VHL protein, which is responsible for HIF-1 (hypoxia-inducible factor-1) dependent cell cycle regulation and cellular pathways mediated by VEGF, PDGF, TGF-α, EPO. The mechanism substantiates the hypoxia dependent vascular tumor growth caused by loss of wild-type VHL protein. The clinical spectrum of vHL syndrome includes multiple tumors of various localization and low histologic grade, often bilateral. The most typical for the syndrome are: hemangioblastoma of central nervous system (typically posterior fossa or medulla), retinal hemangioblastoma, renal cell carcinoma and pheochromocytoma. The aim of the case report is to remind the typical clinical manifestation of von Hippel- Lindau syndrome, update the diagnostic criteria, recommended diagnostic and follow up methods.