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.

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.

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.

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.

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.

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 Lactate as Serum Biomarker for Cardiopulmonary Parameters within the First 24 Hours after a Spontaneous Intracerebral Hemorrhage.

Objective: Cardiopulmonary (CP) complications are well known in patients with an intracerebral hemorrhage (ICH) and could be associated with a higher serum lactate level. The present study aimed to assess the associations between the initial serum lactate level and the CP parameters within the first 24 h of intensive care unit (ICU) treatment in neurosurgical ICH patients. Patients and Methods: A total of 354 patients admitted to the ICU between 01/2009 and 12/2017 with a diagnosis of an ICH were retrospectively analyzed. Blood samples were taken upon admission, and each patient's demographic, medical, and radiological data upon admission, as well as several CP parameters, were recorded within the first 24 h of ICU treatment. Results: A higher serum lactate level was associated with a lower GCS score (p < 0.0001), as well as a higher Acute Physiology and Chronic Health Evaluation II score (p = 0.002) upon admission. Additionally, patients with initially higher serum lactate levels had a significantly higher need for a norepinephrine application (p = 0.004) and inspiratory oxygen fraction (p = 0.03) within the first 24 h. Conclusion: Neurosurgical ICH patients with higher serum lactate levels upon admission require more CP support within the first 24 h of ICU treatment.

Fibrinogen to Albumin Ratio as Early Serum Biomarker for Prediction of Intra-Hospital Mortality in Neurosurgical Intensive Care Unit Patients with Spontaneous Intracerebral Hemorrhage.

Background: The prognostic value of the fibrinogen to albumin ratio on intrahospital mortality has been investigated in patients with cardiovascular disease, cancer, sepsis, and ischemic stroke; however, it has not been investigated for neurosurgical patients with spontaneous intracerebral hemorrhage (ICH). The present study investigates the impact of the fibrinogen to albumin ratio upon admission for intrahospital mortality in neurosurgical intensive care unit (ICU) patients with spontaneous ICH. Methods: A total of 198 patients with diagnosis of spontaneous ICH treated from 10/2008 to 12/2017 at our ICU were retrospectively analyzed. Blood samples were drawn upon admission, and the patients' demographic, medical data, and cranial imaging were collected. Binary logistic regression analysis was performed to identify independent prognostic factors for intrahospital mortality. Results: The total rate of intrahospital mortality was 35.4% (n = 70). In the multivariate regression analysis, higher fibrinogen to albumin ratio (OR = 1.16, CI = 1.02−1.31, p = 0.03) upon admission was an independent predictor of intrahospital mortality in neurosurgical ICU patients with ICH. Moreover, a fibrinogen to albumin ratio cut-off level of >0.075 was related to increased intrahospital mortality (Youden's index = 0.26, sensitivity = 0.51, specificity = 0.77). Conclusion: A fibrinogen to albumin ratio > 0.075 was significantly associated with increased intrahospital mortality in ICH patients.

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.

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.

Integrated Molecular-Morphologic Meningioma Classification: A Multicenter Retrospective Analysis, Retrospectively and Prospectively Validated.

PURPOSE: Meningiomas are the most frequent primary intracranial tumors. Patient outcome varies widely from benign to highly aggressive, ultimately fatal courses. Reliable identification of risk of progression for individual patients is of pivotal importance. However, only biomarkers for highly aggressive tumors are established (CDKN2A/B and TERT), whereas no molecularly based stratification exists for the broad spectrum of patients with low- and intermediate-risk meningioma. METHODS: DNA methylation data and copy-number information were generated for 3,031 meningiomas (2,868 patients), and mutation data for 858 samples. DNA methylation subgroups, copy-number variations (CNVs), mutations, and WHO grading were analyzed. Prediction power for outcome was assessed in a retrospective cohort of 514 patients, validated on a retrospective cohort of 184, and on a prospective cohort of 287 multicenter cases. RESULTS: Both CNV- and methylation family-based subgrouping independently resulted in increased prediction accuracy of risk of recurrence compared with the WHO classification (c-indexes WHO 2016, CNV, and methylation family 0.699, 0.706, and 0.721, respectively). Merging all risk stratification approaches into an integrated molecular-morphologic score resulted in further substantial increase in accuracy (c-index 0.744). This integrated score consistently provided superior accuracy in all three cohorts, significantly outperforming WHO grading (c-index difference P = .005). Besides the overall stratification advantage, the integrated score separates more precisely for risk of progression at the diagnostically challenging interface of WHO grade 1 and grade 2 tumors (hazard ratio 4.34 [2.48-7.57] and 3.34 [1.28-8.72] retrospective and prospective validation cohorts, respectively). CONCLUSION: Merging these layers of histologic and molecular data into an integrated, three-tiered score significantly improves the precision in meningioma stratification. Implementation into diagnostic routine informs clinical decision making for patients with meningioma on the basis of robust outcome prediction.

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.

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.

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.

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.

Early Serum Biomarkers for Intensive Care Unit Treatment within the First 24 Hours in Patients with Intracerebral Hemorrhage.

BACKGROUND: The prognostic significance of serum biomarkers in patients with intracerebral hemorrhage (ICH) is not well investigated concerning inhospital mortality (IHM) and cardiopulmonary events within the first 24 hours of intensive care unit (ICU) treatment. The influence of troponin I (TNI) value and cortisol value (CV) on cardiopulmonary events within the first 24 hours of ICU treatment was reported in subarachnoid hemorrhage patients, but not in ICH patients up to now. The aim of this study was to investigate the role of early serum biomarkers on IHM and TNI value and CV on cardiopulmonary events within the first 24 hours of ICU treatment. PATIENTS AND METHODS: A total of 329 patients with spontaneous ICH were retrospectively analyzed. Blood samples were taken on admission to measure serum biomarkers. The TNI value and CV were defined as biomarkers for cardiopulmonary stress. Demographic data, cardiopulmonary parameters, including norepinephrine application rate (NAR) in microgram per kilogram per minute and inspiratory oxygen fraction (FiO2) within the first 24 hours, and treatment regime were analyzed concerning their impact on ICU treatment and in hospital outcome. Binary logistic analysis was used to identify independent prognostic factors for IHM. RESULTS: Patients with initially nonelevated CVs required higher NAR (p = 0.01) and FiO2 (p = 0.046) within the first 24 hours of ICU treatment. Lower cholinesterase level (p = 0.004), higher NAR (p = 0.002), advanced age (p < 0.0001), larger ICH volume (p < 0.0001), presence of intraventricular hemorrhage (p = 0.007) and hydrocephalus (p = 0.009), raised level of C-reactive protein (p = 0.024), serum lactate (p = 0.003), and blood glucose (p = 0.05) on admission were significantly associated with IHM. In a multivariate model, age (odds ratio [OR]: 1.055; 95% confidence interval [CI]: 1.026-1.085; p < 0.0001), ICH volume (OR: 1.016; CI: 1.008-1.025; p < 0.0001), and Glasgow Coma Scale (GCS) score (OR: 0.680; CI: 0.605-0.764; p < 0.0001) on admission as well as requiring NAR (OR: 1.171; CI: 1.026-1.337; p = 0.02) and FiO2 (OR: 0.951; CI: 0.921-0.983, p = 0.003) within the first 24 hours were independent predictors of IHM. CONCLUSION: Higher levels of C-reactive protein, serum lactate, blood glucose, and lower cholinesterase level on admission were significantly associated with IHM. Patients with initially nonelevated CVs required higher NAR and FiO2 within the first 24 hours of ICU treatment. Furthermore, requiring an NAR > 0.5 µg/kg/min or an FiO2 > 0.21 were identified as additional independent predictors for IHM. These results could be helpful to improve ICU treatment in ICH patients.

Case Report of Complete Radiological Response of a Thalamic Glioblastoma After Treatment With Proton Therapy Followed by Temozolomide and Tumor-Treating Fields.

Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults. We present a case of a 42-year-old male patient presenting with headache and vomiting. Imaging demonstrated obstructive hydrocephalus and a ring-enhancing lesion in the right posterior thalamus. After endoscopic third ventriculostomy and stereotactic biopsy, the histopathologic diagnosis of a malignant glioma was confirmed by DNA methylation array as GBM isocitrate dehydrogenase wild type. The patient was treated with combined treatment of chemoradiation with temozolomide (TMZ) including proton boost, TMZ maintenance, and tumor-treating fields. In this case report, complete radiological response was observed 1 year after the end of radiation therapy.

Impact of Early C-Reactive Protein/Albumin Ratio on Intra-Hospital Mortality Among Patients with Spontaneous Intracerebral Hemorrhage.

OBJECTIVE: The impact of increased C-reactive protein (CRP)/albumin ratio on intra-hospital mortality has been investigated among patients admitted to general intensive care units (ICU). However, it was not investigated among patients with spontaneous intracerebral hemorrhage (ICH). This study aimed to investigate the impact of CRP/albumin ratio on intra-hospital mortality in patients with ICH. PATIENTS AND METHODS: This retrospective study was conducted on 379 ICH patients admitted between 02/2008 and 12/2017. Blood samples were drawn upon admission and the patients' demographic, medical, and radiological data were collected. The identification of the independent prognostic factors for intra-hospital mortality was calculated using binary logistic regression and COX regression analysis. RESULTS: Multivariate regression analysis shows that higher CRP/albumin ratio (odds ratio (OR) = 1.66, 95% confidence interval (CI) = 1.193-2.317, p = 0.003) upon admission is an independent predictor of intra-hospital mortality. Multivariate Cox regression analysis indicated that an increase of 1 in the CRP/albumin ratio was associated with a 15.3% increase in the risk of intra-hospital mortality (hazard ratio = 1.153, 95% CI = 1.005-1.322, p = 0.42). Furthermore, a CRP/albumin ratio cut-off value greater than 1.22 was associated with increased intra-hospital mortality (Youden's Index = 0.19, sensitivity = 28.8, specificity = 89.9, p = 0.007). CONCLUSIONS: A CRP/albumin ratio greater than 1.22 upon admission was significantly associated with intra-hospital mortality in the ICH patients.

Transcranial Doppler Sonography Defined Vasospasm, Ischemic Brain Lesions, and Delayed Ischemic Neurological Deficit in Younger and Elderly Patients after Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Vasospasm, delayed ischemic neurologic deficit (DIND), and ischemic brain lesions after acute subarachnoid hemorrhage (SAH) are associated with increased morbidity and mortality. The purpose of this study was to analyze age cutoffs for vasospasm, DIND, and ischemic brain lesions after SAH. METHODS: This study included 292 aneurysmal SAH patients from January 2005 to December 2015. Patients' data were extracted from a prospective database with measurements of transcranial Doppler sonography. Any vasospasm was defined as a maximum mean flow velocity (MMFV) >120 cm/sec. Severe vasospasms were defined as at least 2 measurements of MMFVs >200 cm/sec or an increase of MMFV >50 cm/sec/24 hours over 2 consecutive days or a new neurologic deficit. All MMFVs >120 cm/sec in absence of severe vasospasm criteria were defined as mild vasospasm. Age-related cutoff values were calculated using receiver operating curve analysis. RESULTS: Any vasospasms occurred in 142 patients and thereof mild vasospasm in 86/142 (60.6%) patients and severe vasospasm in 56/142 patients (39.4%). Significantly higher incidences of any vasospasm (P = 0.005), severe vasospasm (P = 0.003), DIND (P = 0.031), and ischemic brain lesions (P = 0.04) were observed in patients aged <50 years. According to receiver operating curve analysis, the optimal age cutoff was 50 years for the presence of overall vasospasms, severe vasospasms, DIND, and ischemic brain lesions and 65 years for mild vasospasms. CONCLUSIONS: Higher incidences of any vasospasms, severe vasospasms, DIND, and ischemic brain lesions were observed in younger SAH patients.