Oligosarcomas, IDH-mutant are distinct and aggressive.

Oligodendrogliomas are defined at the molecular level by the presence of an IDH mutation and codeletion of chromosomal arms 1p and 19q. In the past, case reports and small studies described gliomas with sarcomatous features arising from oligodendrogliomas, so called oligosarcomas. Here, we report a series of 24 IDH-mutant oligosarcomas from 23 patients forming a distinct methylation class. The tumors were recurrences from prior oligodendrogliomas or developed de novo. Precursor tumors of 12 oligosarcomas were histologically and molecularly indistinguishable from conventional oligodendrogliomas. Oligosarcoma tumor cells were embedded in a dense network of reticulin fibers, frequently showing p53 accumulation, positivity for SMA and CALD1, loss of OLIG2 and gain of H3K27 trimethylation (H3K27me3) as compared to primary lesions. In 5 oligosarcomas no 1p/19q codeletion was detectable, although it was present in the primary lesions. Copy number neutral LOH was determined as underlying mechanism. Oligosarcomas harbored an increased chromosomal copy number variation load with frequent CDKN2A/B deletions. Proteomic profiling demonstrated oligosarcomas to be highly distinct from conventional CNS WHO grade 3 oligodendrogliomas with consistent evidence for a smooth muscle differentiation. Expression of several tumor suppressors was reduced with NF1 being lost frequently. In contrast, oncogenic YAP1 was aberrantly overexpressed in oligosarcomas. Panel sequencing revealed mutations in NF1 and TP53 along with IDH1/2 and TERT promoter mutations. Survival of patients was significantly poorer for oligosarcomas as first recurrence than for grade 3 oligodendrogliomas as first recurrence. These results establish oligosarcomas as a distinct group of IDH-mutant gliomas differing from conventional oligodendrogliomas on the histologic, epigenetic, proteomic, molecular and clinical level. The diagnosis can be based on the combined presence of (a) sarcomatous histology, (b) IDH-mutation and (c) TERT promoter mutation and/or 1p/19q codeletion, or, in unresolved cases, on its characteristic DNA methylation profile.

Tumor treating fields therapy is feasible and safe in a 3-year-old patient with diffuse midline glioma H3K27M - a case report.

Since high grade gliomas are aggressive brain tumors, intensive search for new treatment options is ongoing. For adult patients with newly diagnosed (ndGBM) and recurrent glioblastoma (rGBM), low intensity intermediate frequency alternating electric fields, known as tumor treating fields (TTFields) have been established as a new treatment modality. Tumor treating fields significantly increase survival rates in combination with adjuvant temozolomide (TMZ) in adult and GBM patients. Here, we report about feasibility and safety of treatment on a pediatric patient with diffuse midline glioma who is receiving TTFields therapy in combination with temozolomide.

Proposed definition of competencies for surgical neuro-oncology training.

OBJECTIVE: The aim of this work is to define competencies and entrustable professional activities (EPAs) to be imparted within the framework of surgical neuro-oncological residency and fellowship training as well as the education of medical students. Improved and specific training in surgical neuro-oncology promotes neuro-oncological expertise, quality of surgical neuro-oncological treatment and may also contribute to further development of neuro-oncological techniques and treatment protocols. Specific curricula for a surgical neuro-oncologic education have not yet been established. METHODS: We used a consensus-building approach to propose skills, competencies and EPAs to be imparted within the framework of surgical neuro-oncological training. We developed competencies and EPAs suitable for training in surgical neuro-oncology. RESULT: In total, 70 competencies and 8 EPAs for training in surgical neuro-oncology were proposed. EPAs were defined for the management of the deteriorating patient, the management of patients with the diagnosis of a brain tumour, tumour-based resections, function-based surgical resections of brain tumours, the postoperative management of patients, the collaboration as a member of an interdisciplinary and/or -professional team and finally for the care of palliative and dying patients and their families. CONCLUSIONS AND RELEVANCE: The present work should subsequently initiate a discussion about the proposed competencies and EPAs and, together with the following discussion, contribute to the creation of new training concepts in surgical neuro-oncology.

Serum Biomarkers for Risk Assessment of Intrahospital Transports in Mechanically Ventilated Neurosurgical Intensive Care Unit Patients.

OBJECTIVE: Intrahospital transports (IHTs) of neurosurgical intensive care unit (NICU) patients can be hazardous. Increasing intracranial pressure (ICP) and/or decreasing cerebral perfusion pressure (CPP) as well as cardiopulmonary alterations are common complications of an IHTs, which can lead to secondary brain injury. This study was performed to assess several serum biomarkers concerning their potential to improve safety of IHTs in mechanically ventilated NICU patients. METHODS: All IHTs of mechanically ventilated and sedated NICU patients from 03/2017 to 01/2018 were retrospectively analyzed. Intracranial pressure and CPP measurements were performed in all patients. Serum hemoglobin, hematocrit, and serum sodium were defined as serum biomarkers. Demographic data, computed tomography scan on admission, Simplified Acute Physiology Score and Acute Physiology and Chronic Health Evaluation II, modified Rankin Scale, indication and consequence of IHTs were analyzed. Alteration of ICP/CPP, hemodynamic and pulmonary events were defined as complications. The study population was stratified into patients with the occurrence of a complication and absence of a complication. RESULTS: We analyzed a total number of 184 IHTs in 70 NICU patients with an overall complication rate of 57.6%. Of all, 32.1% IHTs had no direct therapeutic consequence. In patients with higher hemoglobin values prior to IHT less complications occurred, concerning ICP (P = .001), CPP (P = .001), hemodynamic (P = .005), and pulmonary (P < .0001) events. In addition, complications concerning ICP (P = .001), CPP (P = .001), hemodynamic (P = .005), and pulmonary problems (P = .002) were significantly lower in patients with higher hematocrit values before IHT. CONCLUSION: Intrahospital transports of mechanically ventilated NICU patients carry a high risk of increased ICP and hemodynamic complications and should be performed restrictively. Higher values of hemoglobin and hematocrit prior to IHT were associated with less complications with regard to ICP, CPP as well as hemodynamic and pulmonary events and could be helpful to assess the potential risk of complications prior to IHTs.

Preoperative Elevated Levels for Depression, Anxiety, and Subjective Mental Stress Have No Influence on Outcome Measures of Peripheral Nerve Field Stimulation for Chronic Low Back Pain-A Prospective Study.

OBJECTIVE: Peripheral nerve field stimulation (PNFS) is an effective alternative treatment for patients with chronic low back pain. The treatment of low back pain strongly depends on psychological factors like anxiety, depression, and mental stress. The aim of this study was to evaluate the impact of such factors on outcome measures after lead- and implantable pulse generator-implantation. MATERIALS AND METHODS: Between 2014 and 2019, a prospective cohort study of 39 patients with chronic lumbar pain was conducted. Hospital Anxiety and Depression Scale (HADS) score was assessed at baseline to measure symptoms of anxiety and depression. Symptom checklist-90 (SCL-90) was used to measure subjective psychopathology. Pain intensity (numeric pain rating scale [NRS]), SF12v2 with Physical Component Summary and Mental Component Summary (MCS) scores, and Oswestry Disability Index (ODI) were assessed pre- and postoperatively as well as three and six months after PNFS implantation. Outcome values were compared to baseline data. Statistical analysis was performed using depending t-test and analysis of variance (ANOVA). A p value <0.05 was considered significant. RESULTS: The cohort consisted of 39 patients (18 females, 21 males) with a median age of 61 years (IQR25-75  = 52-67 years). NRS, ODI, and SF12v2 showed significant improvement in the whole follow-up period compared to baseline values (p < 0.05). Elevated HADS scores for anxiety were seen in 64.1%, for depression in 76.9% of the patients at baseline. SCL-90 was pathologic in 71.8% of the cases. A one-way ANOVA revealed no differences between elevated HADS- and SCL-90 values and all outcome measures after PNFS implantation in the whole follow-up period (p > 0.05). CONCLUSION: Chronic low back pain is often associated with psychological distress. Our study showed highly elevated levels for anxiety and depression as well as subjective mental stress in patients with chronic low back pain without negative impact on NRS, ODI, and SF12v2 in the whole follow-up after PNFS implantation.

The Predictive Value of Transcutaneous Electrical Nerve Stimulation for Patient Selection in Peripheral Nerve Field Stimulation for Chronic Low Back Pain: A Prospective Study.

OBJECTIVE: Peripheral nerve field stimulation (PNFS) is an effective alternative treatment for patients with chronic low back pain. Transcutaneous electrical nerve stimulation (TENS) is frequently used in pain therapy. Aim of this prospective study was to examine the predictive value of TENS for later PNFS treatment. MATERIALS AND METHODS: Between 2014 and 2019, a prospective cohort study of 41 patients with chronic lumbar pain was conducted. Pain intensity (NRS) was assessed before and after TENS use, preoperatively/postoperatively and in the follow-up after three and six months, SF12v2 questionnaires with physical (PCS) and mental component summary (MCS) scores, and Oswestry disability index (ODI) questionnaire at baseline as well as three and six months after PNFS implantation. Implantation of the PNFS-system with two percutaneous leads was performed after four to seven days of positive testing. Statistical analysis was performed using depending t-test, ANOVA, and Spearman correlation. RESULTS: The cohort consisted of 41 patients (19 females, 22 males) with a median age of 60.5 years (IQR25-75 52-67). Two patients were lost to follow-up. After positive PNFS testing a pulse generator (IPG) was implanted in 15 patients with positive TENS effect and 15 patients without TENS effect. Leads were explanted in nine patients after negative PNFS trial phase. TENS positive patients showed significant correlation to a positive effect in the PNFS trial phase in NRS reduction (p = 0.042) indicating that TENS responders will also respond to PNFS (94% patients). After three and six months follow-up median NRS and SF12v2 (PCS) improved significantly in both cohorts, SF12v2 (MCS) and ODI only in the TENS positive cohort, respectively. CONCLUSION: TENS can be predictive for patient selection in PNFS, as TENS positive patients showed significant correlation with a positive PNFS trial period. Therefore, TENS positive patients might be justifiable to be directly implanted with leads and IPG. TENS positive patients further tend to show a better improvement in the follow-up.

Troponin I as an Early Biomarker of Cardiopulmonary Parameters Within the First 24 Hours After Nontraumatic Subarachnoid Hemorrhage in Intensive Care Unit Patients.

OBJECTIVE: The elevation of serum cardiac troponin I (TNI) in patients with nontraumatic subarachnoid hemorrhage (ntSAH) is a well-known phenomenon. However, the relation between elevated TNI and different cardiopulmonary parameters (CPs) within the first 24 hours after ntSAH is unknown. The present study was conducted to investigate the association between TNI and different CP in patients with ntSAH within the first 24 hours of intensive care unit (ICU) treatment. PATIENTS AND METHODS: We retrospectively analyzed a consecutive group of 117 patients with ntSAH admitted to our emergency department between January 2008 and February 2017. Blood samples were taken to determine TNI values on admission. Demographic data, baseline Glasgow Coma Scale (GCS) score, World Federation of Neurosurgical Societies (WFNS) score, baseline Fisher grade (FG), norepinephrine application rate (NAR) in µg/kg/min, and inspiratory oxygen fraction (OF) were recorded within the first 24 hours. RESULTS: An increased TNI value was found in 32 (27.4%) of 117 patients. There was a significant correlation between initial elevated TNI and a low WFNS score (P = .007), a low GCS score (P = .003) as well as a high OF (P = <.001). The FG (P = .27) and NAR (P = .08) within the first 24 hours of ICU treatment did not show any significant correlation. CONCLUSIONS: In the present study, an increased TNI value was significantly associated with a low WFNS score and GCS score on admission. The TNI was a predictor of the need for a higher OF within the first 24 hours after ntSAH so that TNI could be an informative biomarker to improve ICU therapy.

Programmable valve breakage in shunt systems of children with posthemorrhagic hydrocephalus after minor head trauma-a case series.

PURPOSE: We report five rare cases of programmable valve breakage (Codman Hakim-Medos valve) in shunt systems of children with posthemorrhagic hydrocephalus. Only four similar studies have been published in the current literature. METHODS: Between 2013 and 2018, five children with posthemorrhagic hydrocephalus were admitted to the pediatric department. All patients had a history of slight blows to the head in a minor trauma and follow up MRI scans. After initial clinical examination, cranial computed tomography (CT) and X-ray were conducted. RESULTS: In all cases, pumping the reservoir resulted in very slow refilling. The cranial CT in one patient showed slit ventricles confirming the suspicion of overdrainage, the other cases a slight enhancement of the hydrocephalus. In lateral X-rays of the skull in comparison to the first X-ray control of the shunt valve, the pressure control chamber could be seen dislocated in the inferior part of the reservoir in all cases. Surgery revealed that the shunt valve was broken. The pressure control chamber had dropped to the bottom of the reservoir. After implantation of a new shunt valve, the symptoms resolved completely in all five children. Overall this complication occurred in 4.3% (5 of 85 implanted Codman Hakim-Medos valve) of all children necessitating ventriculoperitoneal shunt implantation between January 2013 and December 2018. CONCLUSION: The well-accepted Codman Hakim-Medos programmable valve is part of a tube-system, which is designed to offer the possibility of a reliable and precise treatment of hydrocephalus. Various mechanical and non-mechanical complications of shunt systems have been reported. Valve breakage is a very rare condition, often missed, and must be kept in mind when trauma and prior MRI scan are reported.

A Retrospective Analysis of 25 Cases With Peripheral Nerve Field Stimulation for Chronic Low Back Pain and the Predictive Value of Transcutaneous Electrical Nerve Stimulation for Patient Selection.

OBJECTIVE: Transcutaneous electrical nerve stimulation (TENS) and peripheral nerve field stimulation (PNFS) may be proposed to patients with chronic lumbar pain refractory to conventional treatment. Aim of this study was to assess the importance of preoperatively treatment with TENS as a predictive value for later successful PNFS and impact of PNFS in follow-up of 12 months. METHODS: Between 2012 and 2016, a retrospective analysis of 25 patients with chronic lumbar pain and implantation of a PNFS-system was performed. Pain intensity (NRS), health-related quality of life (EQ-5D-5L), Oswestry disability index (ODI), actual mood state scale (ASTS), and treatment satisfaction (CSQ-8) were assessed pre/postoperatively, after 6 and 12 months. TENS use before surgery was assessed. RESULTS: The cohort consisted of 25 patients with a median age of 56 years (IQR25-75 51-63). In a subgroup analysis, 18 patients used TENS before surgery, 7 did not use TENS and were excluded. No pain relief was observed in 14 patients. Ten of these patients showed later positive effect in PNFS trial stimulation. In four patients, pain relief with TENS was seen. One patient later on had no benefit after PNFS trial, three had sufficient pain relief. In the whole cohort, five patients had no benefit after PNFS trial, in 20 patients a neurostimulator was implanted. NRS, EQ-5D-5L, and ODI measures showed significant improvement in the whole follow-up after PNFS implantation. ASTS scale showed an increase of values for positive mood and a reduction in values for sorrow, fatigue, and anger. In 55%, a sustained reduction in demand for analgesics was seen after 6 months, 50% after 12 months, respectively. CONCLUSION: In this retrospective analysis, TENS has no predictive value in the selection of patients with low back pain for the PFNS treatment. PNFS is effective and safe to relieve significantly symptoms of chronic low back pain.

Microsurgical unilateral laminotomy for decompression of lumbar spinal stenosis: long-term results and predictive factors.

BACKGROUND: The microsurgical unilateral laminotomy (MUL) technique for bilateral decompression of lumbar spinal stenosis (LSS) is a less destabilizing alternative to laminectomy and leads to good short-term outcomes. However, little is known about the long-term results including predictive factors. METHODS: Medical records of patients who underwent MUL for LSS decompression between 2005 and 2010 were reviewed, and a questionnaire was distributed to complement the long-term outcome data. The study population consisted of 176 patients including 17 patients with stable grade I spondylolisthesis. Complications and reoperations were meticulously analyzed. Clinical outcome was measured using a modified Prolo scale and was further dichotomized in good vs. poor outcome. Predictive factors were obtained from uni- and multivariate analyses. RESULTS: The median age of the cohort was 70.0 years and the follow-up 71.7 months. Complications occurred in 5.1 % of the patients. The overall reoperation rate was 17.0 %, including surgery, which was exclusively performed at other levels in 4.0 %. The reoperation rate for fusion was 4.5 %. Good neurogenic claudication outcome faded from 98.3 % at hospital discharge to 47.2 % at 6 years. Multivariate analysis identified previous lumbar operation as a potential independent predictor of a reoperation; potential independent predictors of poor long-term claudication outcome were older age, female gender, higher body mass index (BMI) and tobacco smoking. CONCLUSIONS: In our experience, the long-term reoperation rate after MUL for LSS is not negligible and higher in previously operated patients. It seems like the good initial clinical results after MUL may fade over time, and several patient-related predictive factors including potentially modifiable obesity and tobacco smoking seem to play an important role.

Predicting the "usefulness" of 5-ALA-derived tumor fluorescence for fluorescence-guided resections in pediatric brain tumors: a European survey.

BACKGROUND: Five-aminolevulinic acid (Gliolan, medac, Wedel, Germany, 5-ALA) is approved for fluorescence-guided resections of adult malignant gliomas. Case reports indicate that 5-ALA can be used for children, yet no prospective study has been conducted as of yet. As a basis for a study, we conducted a survey among certified European Gliolan users to collect data on their experiences with children. METHODS: Information on patient characteristics, MRI characteristics of tumors, histology, fluorescence qualities, and outcomes were requested. Surgeons were further asked to indicate whether fluorescence was "useful", i.e., leading to changes in surgical strategy or identification of residual tumor. Recursive partitioning analysis (RPA) was used for defining cohorts with high or low likelihoods for useful fluorescence. RESULTS: Data on 78 patients <18 years of age were submitted by 20 centers. Fluorescence was found useful in 12 of 14 glioblastomas (85 %), four of five anaplastic astrocytomas (60 %), and eight of ten ependymomas grades II and III (80 %). Fluorescence was found inconsistently useful in PNETs (three of seven; 43 %), gangliogliomas (two of five; 40 %), medulloblastomas (two of eight, 25 %) and pilocytic astrocytomas (two of 13; 15 %). RPA of pre-operative factors showed tumors with supratentorial location, strong contrast enhancement and first operation to have a likelihood of useful fluorescence of 64.3 %, as opposed to infratentorial tumors with first surgery (23.1 %). CONCLUSIONS: Our survey demonstrates 5-ALA as being used in pediatric brain tumors. 5-ALA may be especially useful for contrast-enhancing supratentorial tumors. These data indicate controlled studies to be necessary and also provide a basis for planning such a study.

Prediction of Initial CRP/Albumin Ratio on In-Hospital Mortality in Isolated Traumatic Brain Injury Patients.

The CRP/albumin ratio (CAR) is a mortality predictor in intensive care unit (ICU) patients. The aim of the current study was to investigate the ability of CAR to predict in-hospital mortality (IHM) in patients with isolated traumatic brain injury (iTBI). We performed a retrospective analysis including 200 patients with iTBI admitted to our neurosurgical intensive care unit (NICU) between September 2014 and December 2016. Serum biomarkers, demographic and radiological data, several ICU scores, and cardiopulmonary parameters were analyzed. The rate of IHM was 27.5% (55/200) and significantly associated with a higher AIS head score (p < 0.0001), a lower albumin level (p < 0.0001), and the necessity of a higher level of inspiratory oxygen fraction (p = 0.002). Furthermore, advanced age (odds ratio [OR] = 0.953, 95% confidence interval [CI] = 0.927-0.981, p = 0.001), a lower GCS score (OR = 1.347, 95% CI = 1.203-1.509, p < 0.0001), a higher level of lactate (OR = 0.506, 95% CI = 0.353-0.725, p < 0.0001), a higher CAR (OR = 0.547, 95% CI = 0.316-0.945, p = 0.031) and a higher norepinephrine application rate (OR = 0.000, 95% CI 0.000-0.090, p = 0.016) were identified as independent predictors of IHM. ROC analysis showed an association between IHM and a CAR cut-off value of >0.38 (Youden index 0.073, sensitivity: 27.9, specificity: 64.8, p = 0.044). We could identify a CAR > 0.38 as a new independent predictor for IHM in patients with iTBI.

DistSNE: Distributed computing and online visualization of DNA methylation-based central nervous system tumor classification.

The current state-of-the-art analysis of central nervous system (CNS) tumors through DNA methylation profiling relies on the tumor classifier developed by Capper and colleagues, which centrally harnesses DNA methylation data provided by users. Here, we present a distributed-computing-based approach for CNS tumor classification that achieves a comparable performance to centralized systems while safeguarding privacy. We utilize the t-distributed neighborhood embedding (t-SNE) model for dimensionality reduction and visualization of tumor classification results in two-dimensional graphs in a distributed approach across multiple sites (DistSNE). DistSNE provides an intuitive web interface (https://gin-tsne.med.uni-giessen.de) for user-friendly local data management and federated methylome-based tumor classification calculations for multiple collaborators in a DataSHIELD environment. The freely accessible web interface supports convenient data upload, result review, and summary report generation. Importantly, increasing sample size as achieved through distributed access to additional datasets allows DistSNE to improve cluster analysis and enhance predictive power. Collectively, DistSNE enables a simple and fast classification of CNS tumors using large-scale methylation data from distributed sources, while maintaining the privacy and allowing easy and flexible network expansion to other institutes. This approach holds great potential for advancing human brain tumor classification and fostering collaborative precision medicine in neuro-oncology.

Serum biomarkers for risk assessment of intrahospital transports in neurosurgical intensive care unit patients.

BACKGROUND: Intrahospital transport (IHT) of Neurosurgical Intensive Care Unit (NICU) patients for cranial computed tomography (CCT) scans is associated with a high rate of complications. The potential of serum biomarkers to estimate the risk for complications associated with IHT and improve their safety remains underexplored. The present study investigated the influence of several serum biomarkers on IHT-associated complications in brain-injured NICU patients. METHODS: A total of 523 IHTs in 223 NICU patients were prospectively analyzed (05/2019-05/2020). Hemoglobin, hematocrit, serum sodium, and albumin levels were evaluated as serum biomarkers. Each patient's demographic data, CCT scan, NICU parameters and modified Rankin Scale at discharge as well as indications, consequences, and complications of IHTs were analyzed. RESULTS: In 58.7% of all IHTs, at least one IHT-associated complication was observed with 60.1% of all IHTs having no therapeutic consequence. Significantly lower rates of increased intracranial pressure (ICP; P<0.0001), decreased cerebral perfusion pressure (CPP; P=0.03) as well as hemodynamic (P<0.0001) and pulmonary events (P=0.01) were observed in patients with higher hemoglobin levels prior to IHT. Additionally, higher hematocrit levels before IHT were associated with a fewer rate of hemodynamic (P<0.0001), pulmonary (P=0.006), ICP (P<0.0001), and CPP (P=0.01) events. CONCLUSIONS: Higher levels of hemoglobin and hematocrit are associated with less complications with respect to ICP, CPP, hemodynamic and pulmonary events during IHT in NICU patients. Therefore, these biomarkers may be helpful for risk assessment of potential complications prior to IHT.

Serum Urea-to-Albumin Ratio Is an Independent Predictor of Intra-Hospital Mortality in Neurosurgical Intensive Care Unit Patients with Spontaneous Intracerebral Hemorrhage.

The negative prognostic value of an increased serum urea-to-albumin ratio on intra-hospital mortality is frequently investigated in general critically ill patients and patients with septic shock, although not in neurosurgical patients with spontaneous intracerebral hemorrhages (ICH). The current study was conducted to investigate the impact of the serum urea-to-albumin ratio upon hospital admission on intra-hospital mortality in ICU-admitted neurosurgical patients with spontaneous ICH. METHODS: This retrospective study analyzed 354 ICH patients, who were treated from 10/2008 to 12/2017 at our intensive care units (ICU). Blood samples were taken upon admission, and the patients' demographic, medical, and radiological data were analyzed. A binary logistic regression analysis was performed for the identification of independent prognostic parameters for intra-hospital mortality. RESULTS: Overall, the intra-hospital mortality rate was 31.4% (n = 111). In the binary logistic analysis, a higher serum urea-to-albumin ratio (OR = 1.9, CI = 1.23-3.04, p = 0.005) upon admission was identified as an independent predictor of intra-hospital mortality. Furthermore, a serum urea-to-albumin ratio cut-off level of >0.01 was associated with raised intra-hospital mortality (Youden's index = 0.32, sensitivity = 0.57, specificity = 0.25). CONCLUSION: A serum urea-to-albumin ratio greater than 1.1 seems to be a prognostic marker to predict intra-hospital mortality in patients with ICH.

Impact of Serum Lactate as an Early Serum Biomarker for Cardiopulmonary Parameters within the First 24 Hours of Intensive Care Unit Treatment in Patients with Isolated Traumatic Brain Injury.

OBJECTIVE: Cardiopulmonary (CP) complications are well-known phenomena in patients with isolated traumatic brain injury (iTBI) that can lead to tissue hypoperfusion and hypoxia. Serum lactate level is a well-known biomarker, indicating these systemic dysregulations in various diseases, but this has not been investigated in iTBI patients so far. The current study evaluates the association between serum lactate levels upon admission and CP parameters within the first 24 h of intensive care unit (ICU) treatment in iTBI patients. PATIENTS AND METHODS: 182 patients with iTBI who were admitted to our neurosurgical ICU between December 2014 and December 2016 were retrospectively evaluated. Serum lactate levels on admission, demographic, medical, and radiological data upon admission, as well as several CP parameters within the first 24 h of ICU treatment, were analyzed, as well as the functional outcome at discharge. The total study population was dichotomized into patients with an elevated serum lactate level (lactate-positive) and patients with a low serum lactate level (lactate-negative) upon admission. RESULTS: 69 patients (37.9%) had an elevated serum lactate level upon admission, which was significantly associated with a lower Glasgow Coma Scale score (p = 0.04), a higher head AIS score (p = 0.03), and a higher Acute Physiology and Chronic Health Evaluation II score (p = 0.01) upon admission, as well as a higher modified Rankin Scale score (p = 0.002) and a lower Glasgow Outcome Scale score (p < 0.0001) at discharge. Furthermore, the lactate-positive group required a significantly higher norepinephrine application rate (NAR; p = 0.04) and a higher fraction of inspired oxygen (FiO2; p = 0.04) to maintain the defined CP parameters within the first 24 h. CONCLUSION: ICU-admitted iTBI patients with elevated serum lactate levels upon admission required higher CP support within the first 24 h of ICU treatment after iTBI. Serum lactate may be a helpful biomarker for improving ICU treatment in the early stages.

Significantly higher expression of high-mobility group AT hook protein 2 (HMGA2) in the border zone of glioblastoma.

BACKGROUND: High-mobility group AT-hook protein 2 (HMGA2) is a gene regulatory protein that is correlated with metastatic potential and poor prognosis. It has been shown that HMGA2 is overexpressed in various tumors such as lung cancer or pancreatic cancer. The invasive character and highly aggressive structure of glioblastoma let us to investigate HMGA2 expression in the border zone of the tumor more closely. We compared HMGA2 expression between glioblastoma and normal brain tissue. In addition, we analyzed and compared HMGA2 expression in the border and center zones of tumors. Correlation tests between HMGA expression and clinical parameters such as MGMT-status and survival were performed. METHODS: Samples from 23 patients with WHO grade 4 glioblastomas were analyzed for HMGA2 expression using quantitative real-time polymerase chain reaction (qPCR) and immunohistochemistry (IHC) and correlated with clinical parameters. The areas from the tumor center and border were analyzed separately. Two normal brain tissue specimens were used as the controls. RESULTS: Our results confirm that HMGA2 is higher expressed in glioblastoma compared to healthy brain tissue (qPCR, P=0.013; IHC, P=0.04). Moreover, immunohistochemistry revealed significantly higher HMGA2 expression in the border zone of the tumor than in the tumor center zone (P=0.012). Survival analysis revealed a tendency for shorter survival when HMGA2 was highly expressed in the border zone. CONCLUSIONS: The results reveal an overexpression of HMGA2 in the border zone of glioblastomas; thus, the expression cluster of HMGA2 seems to be heterogenous and thorough borough surgical resection of the vital and aggressive border cells might be important to inhibit the invasive character of the tumor.

Leveraging Attention-Based Convolutional Neural Networks for Meningioma Classification in Computational Histopathology.

Convolutional neural networks (CNNs) are becoming increasingly valuable tools for advanced computational histopathology, promoting precision medicine through exceptional visual decoding abilities. Meningiomas, the most prevalent primary intracranial tumors, necessitate accurate grading and classification for informed clinical decision-making. Recently, DNA methylation-based molecular classification of meningiomas has proven to be more effective in predicting tumor recurrence than traditional histopathological methods. However, DNA methylation profiling is expensive, labor-intensive, and not widely accessible. Consequently, a digital histology-based prediction of DNA methylation classes would be advantageous, complementing molecular classification. In this study, we developed and rigorously assessed an attention-based multiple-instance deep neural network for predicting meningioma methylation classes using tumor methylome data from 142 (+51) patients and corresponding hematoxylin-eosin-stained histological sections. Pairwise analysis of sample cohorts from three meningioma methylation classes demonstrated high accuracy in two combinations. The performance of our approach was validated using an independent set of 51 meningioma patient samples. Importantly, attention map visualization revealed that the algorithm primarily focuses on tumor regions deemed significant by neuropathologists, offering insights into the decision-making process of the CNN. Our findings highlight the capacity of CNNs to effectively harness phenotypic information from histological sections through computerized images for precision medicine. Notably, this study is the first demonstration of predicting clinically relevant DNA methylome information using computer vision applied to standard histopathology. The introduced AI framework holds great potential in supporting, augmenting, and expediting meningioma classification in the future.

Intracerebral hemorrhage in the very old: future demographic trends of an aging population.

BACKGROUND AND PURPOSE: In most European societies and in the United States, the percentage of patients ≥80 years has been rising over the past century. The present study was conducted to observe this demographic change and its impact on patients with intracerebral hemorrhage (ICH). METHODS: We reviewed patients' data with the diagnosis of ICH from January 2007 to December 2009. All data were collected out of a prospective stroke registry covering the entire state of Hesse, Germany. Incidence rates and absolute numbers of patients with ICH for 2009 to 2050 were calculated. RESULTS: Of 3448 patients, 34% had an age ≥80 years. Hospital mortality was 35.9% for patients ≥80 years and 20.0% for patients <80 years. Unfavorable outcome (modified Rankin Scale score >2) was more often found in patients ≥80 years compared with patients <80 years (84.9% versus 74.8%). By the year 2050, the proportion of all patients with ICH ≥80 years will be 2.5-fold higher than in 2009. The total number of ICH cases will increase approximately 35.2% assuming that ICH probability stays the same. The number of patients who die in the hospital will increase approximately 60.2%. The total number of patients with severe disability due to ICH will increase approximately 36.8%. CONCLUSIONS: If current treatment strategies according to age remain unchanged, an increase of in-hospital mortality and a higher proportion of patients who need lifelong care after ICH can be expected in the coming decades.

Cerebrospinal fluid lactate concentration after withdrawal of metabolic suppressive therapy in subarachnoid hemorrhage.

Hyperglycolysis is a known phenomenon after severe subarachnoid hemorrhage (SAH) and after brain injury. It is characterized by decreased oxidative metabolism and relatively increased anaerobic glycolysis. Metabolic suppressive therapy reduces the cerebral metabolic rate of oxygen (CMRO(2)) and the cerebral metabolic rate of glucose (CMRGluc). If CMRO(2) is suppressed after SAH, withdrawal of metabolic suppressive therapy could lead to the accumulation of lactate. In this project, we assessed the relationship between the withdrawal of metabolic suppressive therapy and cerebrospinal fluid (CSF) lactate concentration. A prospective observational database containing 262 patients with SAH was retrospectively analyzed. CSF lactate levels were compared with the daily dose of metabolic suppressive therapy. Outcome was assessed with the Glasgow Outcome Scale (GOS). In 56% of patients an increase in CSF lactate (mean: 3.2 ± 0.9 mmol/L) after withdrawal of metabolic suppressive therapy was observed. Mean Glasgow Outcome Score (GOS) was lower in patients with an increase in CSF lactate concentration (>0.5 mmol/L) after withdrawal of metabolic suppressive therapy (p = 0.095). In 88% of patients who died during the first 30 days after SAH, a CSF lactate elevation of more than 0.5 mmol/L after withdrawal of metabolic suppressive therapy was found (p = 0.071).