The glioblastoma multiforme tumor site promotes the commitment of tumor-infiltrating lymphocytes to the TH17 lineage in humans.

Although glioblastoma multiforme (GBM) is not an invariably cold tumor, checkpoint inhibition has largely failed in GBM. In order to investigate T cell-intrinsic properties that contribute to the resistance of GBM to endogenous or therapeutically enhanced adaptive immune responses, we sorted CD4+ and CD8+ T cells from the peripheral blood, normal-appearing brain tissue, and tumor bed of nine treatment-naive patients with GBM. Bulk RNA sequencing of highly pure T cell populations from these different compartments was used to obtain deep transcriptomes of tumor-infiltrating T cells (TILs). While the transcriptome of CD8+ TILs suggested that they were partly locked in a dysfunctional state, CD4+ TILs showed a robust commitment to the type 17 T helper cell (TH17) lineage, which was corroborated by flow cytometry in four additional GBM cases. Therefore, our study illustrates that the brain tumor environment in GBM might instruct TH17 commitment of infiltrating T helper cells. Whether these properties of CD4+ TILs facilitate a tumor-promoting milieu and thus could be a target for adjuvant anti-TH17 cell interventions needs to be further investigated.

High Prevalence and Clinical Relevance of Intrapulmonary Vascular Dilatations in Patients Undergoing TIPS Implantation.

BACKGROUND & AIMS: Considerate patient selection is vital to ensure the best possible outcomes after transjugular intrahepatic portosystemic shunt (TIPS) insertion. However, data regarding the impact of intrapulmonary vascular dilatations (IPVDs) or hepatopulmonary syndrome (HPS) on the clinical course after TIPS implantation is lacking. Hence, this study aimed to investigate the relevance of IPVD and HPS in patients undergoing TIPS implantation. METHODS: Contrast enhanced echocardiography and blood gas analysis were utilized to determine presence of IPVD and HPS. Multivariable competing risk analyses were performed to evaluate cardiac decompensation (CD), hepatic decompensation (HD), and liver transplant (LTx)-free survival within 1 year of follow-up. RESULTS: Overall, 265 patients were included, of whom 136 had IPVD and 71 fulfilled the HPS criteria. Patients with IPVD had lower Freiburg index of post-TIPS survival (FIPS) scores, lower creatinine, and more often received TIPS because of variceal bleeding. Presence of IPVD was associated with a significantly higher incidence of CD (hazard ratio [HR], 1.756; 95% confidence interval [CI], 1.011-3.048; P = .046) and HD (HR, 1.841; 95% CI, 1.255-2.701; P = .002). However, LTx-free survival was comparable between patients with and without IPVD (HR, 1.081; 95% CI, 0.630-1.855; P = .780). Patients with HPS displayed a trend towards more CD (HR, 1.708; 95% CI, 0.935-3.122; P = .082) and HD (HR, 1.458; 95% CI, 0.934-2.275; P = .097) that failed to reach statistical significance. LTx-free survival did not differ in those with HPS compared with patients without HPS, respectively (HR, 1.052; 95% CI, 0.577-1.921; P = .870). CONCLUSION: Screening for IPVD before TIPS implantation could help to further identify patients at higher risk of CD and HD.

Motor mapping of the hand muscles using peripheral innervation-based navigated transcranial magnetic stimulation to identify functional reorganization of primary motor regions in malignant tumors.

Tumor-related motor reorganization remains unclear. Navigated transcranial magnetic stimulation (nTMS) can investigate plasticity non-invasively. nTMS-induced motor-evoked potentials (MEPs) of different muscles are commonly used to measure the center of gravity (CoG), the location with the highest density of corticospinal neurons in the precentral gyrus. We hypothesized that a peripheral innervation-based MEP analysis could outline the tumor-induced motor reorganization with a higher clinical and oncological relevance. Then, 21 patients harboring tumors inside the left corticospinal tract (CST) or precentral gyrus were enrolled in group one (G1), and 24 patients with tumors outside the left CST or precentral gyrus were enrolled in Group 2 (G2). Median- and ulnar-nerve-based MEP analysis combined with diffusion tensor imaging fiber tracking was used to explore motor function distribution. There was no significant difference in CoGs or size of motor regions and underlying tracts between G1 and G2. However, G1 involved a sparser distribution of motor regions and more motor-positive sites in the supramarginal gyrus-tumors inside motor areas induced motor reorganization. We propose an "anchor-and-ship theory" hypothesis for this process of motor reorganization: motor CoGs are stably located in the cortical projection area of the CST, like a seated anchor, as the core area for motor output. Primary motor regions can relocate to nearby gyri via synaptic plasticity and association fibers, like a ship moving around its anchor. This principle can anticipate functional reorganization and be used as a neuro-oncological tool for local therapy, such as radiotherapy or surgery.

Radiotherapy concepts for spinal metastases-results from an online survey among radiation oncologists of the German Society for Radiation Oncology.

PURPOSE: Spinal metastases (SM) are a common radiotherapy (RT) indication. There is limited level I data to drive decision making regarding dose regimen (DR) and target volume definition (TVD). We aim to depict the patterns of care for RT of SM among German Society for Radiation Oncology (DEGRO) members. METHODS: An online survey on conventional RT and Stereotactic Body Radiation Therapy (SBRT) for SM, distributed via e­mail to all DEGRO members, was completed by 80 radiation oncologists between February 24 and April 29, 2022. Participation was voluntary and anonymous. RESULTS: A variety of DR was frequently used for conventional RT (primary: n = 15, adjuvant: n = 14). 30 Gy/10 fractions was reported most frequently. TVD in adjuvant RT was heterogenous, with a trend towards larger volumes. SBRT was offered in 65% (primary) and 21% (adjuvant) of participants' institutions. A variety of DR was reported (primary: n = 40, adjuvant: n = 27), most commonly 27 Gy/3 fractions and 30 Gy/5 fractions. 59% followed International Consensus Guidelines (ICG) for TVD. CONCLUSION: We provide a representative depiction of RT practice for SM among DEGRO members. DR and TVD are heterogeneous. SBRT is not comprehensively practiced, especially in the adjuvant setting. Further research is needed to provide a solid data basis for detailed recommendations.

Resolving spatial response heterogeneity in glioblastoma.

PURPOSE: Spatial intratumoral heterogeneity poses a significant challenge for accurate response assessment in glioblastoma. Multimodal imaging coupled with advanced image analysis has the potential to unravel this response heterogeneity. METHODS: Based on automated tumor segmentation and longitudinal registration with follow-up imaging, we categorized contrast-enhancing voxels of 61 patients with suspected recurrence of glioblastoma into either true tumor progression (TP) or pseudoprogression (PsP). To allow the unbiased analysis of semantically related image regions, adjacent voxels with similar values of cerebral blood volume (CBV), FET-PET, and contrast-enhanced T1w were automatically grouped into supervoxels. We then extracted first-order statistics as well as texture features from each supervoxel. With these features, a Random Forest classifier was trained and validated employing a 10-fold cross-validation scheme. For model evaluation, the area under the receiver operating curve, as well as classification performance metrics were calculated. RESULTS: Our image analysis pipeline enabled reliable spatial assessment of tumor response. The predictive model reached an accuracy of 80.0% and a macro-weighted AUC of 0.875, which takes class imbalance into account, in the hold-out samples from cross-validation on supervoxel level. Analysis of feature importances confirmed the significant role of FET-PET-derived features. Accordingly, TP- and PsP-labeled supervoxels differed significantly in their 10th and 90th percentile, as well as the median of tumor-to-background normalized FET-PET. However, CBV- and T1c-related features also relevantly contributed to the model's performance. CONCLUSION: Disentangling the intratumoral heterogeneity in glioblastoma holds immense promise for advancing precise local response evaluation and thereby also informing more personalized and localized treatment strategies in the future.

The role of molecular tumor boards in neuro-oncology: a nationwide survey.

BACKGROUND: In neuro-oncology, the inclusion of tumor patients in the molecular tumor board has only become increasingly widespread in recent years, but so far there are no standards for indication, procedure, evaluation, therapy recommendations and therapy implementation of neuro-oncological patients. The present work examines the current handling of neuro-oncological patients included in molecular tumor boards in Germany. METHODS: We created an online based survey with questions covering the handling of neuro-oncologic patient inclusion, annotation of genetic analyses, management of target therapies and the general role of molecular tumor boards in neuro-oncology in Germany. We contacted all members of the Neuro-Oncology working group (NOA) of the German Cancer Society (DKG) by e-mail. RESULTS: 38 responses were collected. The majority of those who responded were specialists in neurosurgery or neurology with more than 10 years of professional experience working at a university hospital. Molecular tumor boards (MTB) regularly take place once a week and all treatment disciplines of neuro-oncology patients take part. The inclusions to the MTB are according to distinct tumors and predominantly in case of tumor recurrence. An independently MTB member mostly create the recommendations, which are regularly implemented in the tumor treatment. Recommendations are given for alteration classes 4 and 5. Problems exist mostly within the cost takeover of experimental therapies. The experimental therapies are mostly given in the department of medical oncology. CONCLUSIONS: Molecular tumor boards for neuro-oncological patients, by now, are not standardized in Germany. Similarities exists for patient inclusion and interpretation of molecular alterations; the time point of inclusion and implementation during the patient treatment differ between the various hospitals. Further studies for standardization and harmonisation are needed. In summary, most of the interviewees envision great opportunities and possibilities for molecular-based neuro-oncological therapy in the future.

Functional connectivity signatures of major depressive disorder: machine learning analysis of two multicenter neuroimaging studies.

The promise of machine learning has fueled the hope for developing diagnostic tools for psychiatry. Initial studies showed high accuracy for the identification of major depressive disorder (MDD) with resting-state connectivity, but progress has been hampered by the absence of large datasets. Here we used regular machine learning and advanced deep learning algorithms to differentiate patients with MDD from healthy controls and identify neurophysiological signatures of depression in two of the largest resting-state datasets for MDD. We obtained resting-state functional magnetic resonance imaging data from the REST-meta-MDD (N = 2338) and PsyMRI (N = 1039) consortia. Classification of functional connectivity matrices was done using support vector machines (SVM) and graph convolutional neural networks (GCN), and performance was evaluated using 5-fold cross-validation. Features were visualized using GCN-Explainer, an ablation study and univariate t-testing. The results showed a mean classification accuracy of 61% for MDD versus controls. Mean accuracy for classifying (non-)medicated subgroups was 62%. Sex classification accuracy was substantially better across datasets (73-81%). Visualization of the results showed that classifications were driven by stronger thalamic connections in both datasets, while nearly all other connections were weaker with small univariate effect sizes. These results suggest that whole brain resting-state connectivity is a reliable though poor biomarker for MDD, presumably due to disease heterogeneity as further supported by the higher accuracy for sex classification using the same methods. Deep learning revealed thalamic hyperconnectivity as a prominent neurophysiological signature of depression in both multicenter studies, which may guide the development of biomarkers in future studies.

Adjuvant re-irradiation vs. no early re-irradiation of resected recurrent glioblastoma: pooled comparative cohort analysis from two tertiary centers.

BACKGROUND: The optimal management strategy for recurrent glioblastoma (rGBM) remains uncertain, and the impact of re-irradiation (Re-RT) on overall survival (OS) is still a matter of debate. This study included patients who achieved gross total resection (GTR) after a second surgery after recurrence, following the GlioCave criteria. METHODS: Inclusion criteria include being 18 years or older, having histologically confirmed locally recurrent IDHwt or IDH unknown GBM, achieving MRI-proven GTR after the second surgery, having a Karnofsky performance status of at least 60% after the second surgery, having a minimum interval of 6 months between the first radiotherapy and the second surgery, and a maximum of 8 weeks from second surgery to the start of Re-RT. RESULTS: A total of 44 patients have met the inclusion criteria. The median OS after the second surgery was 14 months. All patients underwent standard treatment after initial diagnosis, including maximum safe resection, adjuvant radiochemotherapy and adjuvant chemotherapy. Re-RT did not significantly impact OS. However, MGMT promoter methylation status and a longer interval (> 12 months) between treatments were associated with better OS. Multivariate analysis revealed the MGMT status as the only significant predictor of OS. CONCLUSION: Factors such as MGMT promoter methylation status and treatment interval play crucial roles in determining patient outcomes after second surgery. Personalized treatment strategies should consider these factors to optimize the management of rGBM. Prospective research is needed to define the value of re-RT after second surgery and to inform decision making in this situation.

Treatment outcome of IDH1/2 wildtype CNS WHO grade 4 glioma histologically diagnosed as WHO grade II or III astrocytomas.

BACKGROUND: Isocitrate dehydrogenase (IDH)1/2 wildtype (wt) astrocytomas formerly classified as WHO grade II or III have significantly shorter PFS and OS than IDH mutated WHO grade 2 and 3 gliomas leading to a classification as CNS WHO grade 4. It is the aim of this study to evaluate differences in the treatment-related clinical course of these tumors as they are largely unknown. METHODS: Patients undergoing surgery (between 2016-2019 in six neurosurgical departments) for a histologically diagnosed WHO grade 2-3 IDH1/2-wt astrocytoma were retrospectively reviewed to assess progression free survival (PFS), overall survival (OS), and prognostic factors. RESULTS: This multi-center study included 157 patients (mean age 58 years (20-87 years); with 36.9% females). The predominant histology was anaplastic astrocytoma WHO grade 3 (78.3%), followed by diffuse astrocytoma WHO grade 2 (21.7%). Gross total resection (GTR) was achieved in 37.6%, subtotal resection (STR) in 28.7%, and biopsy was performed in 33.8%. The median PFS (12.5 months) and OS (27.0 months) did not differ between WHO grades. Both, GTR and STR significantly increased PFS (P < 0.01) and OS (P < 0.001) compared to biopsy. Treatment according to Stupp protocol was not associated with longer OS or PFS compared to chemotherapy or radiotherapy alone. EGFR amplification (P = 0.014) and TERT-promotor mutation (P = 0.042) were associated with shortened OS. MGMT-promoter methylation had no influence on treatment response. CONCLUSIONS: WHO grade 2 and 3 IDH1/2 wt astrocytomas, treated according to the same treatment protocols, have a similar OS. Age, extent of resection, and strong EGFR expression were the most important treatment related prognostic factors.

Permanent deterioration of fine motor skills after the resection of tumors in the supplementary motor area.

Supplementary motor area syndrome (SMAS) represents a common neurosurgical sequela. The incidence and time frame of its occurrence have yet to be characterized after surgery for brain tumors. We examined patients suffering from a brain tumor preoperatively, postoperatively, and during follow-up examinations after three months, including fine motor skills testing and transcranial magnetic stimulation (TMS). 13 patients suffering from a tumor in the dorsal part of the superior frontal gyrus underwent preoperative, early postoperative, and 3-month follow-up testing of fine motor skills using the Jebsen-Taylor Hand Function Test (JHFT) and the Nine-Hole Peg Test (NHPT) consisting of 8 subtests for both upper extremities. They completed TMS for cortical motor function mapping. Test completion times (TCTs) were recorded and compared. No patient suffered from neurological deficits before surgery. On postoperative day one, we detected motor deficits in two patients, which remained clinically stable at a 3-month follow-up. Except for page-turning, every subtest indicated a significant worsening of function, reflected by longer TCTs (p < 0.05) in the postoperative examinations for the contralateral upper extremity (contralateral to the tumor manifestation). At 3-month follow-up examinations for the contralateral upper extremity, each subtest indicated significant worsening compared to the preoperative status despite improvement to the immediate postoperative level. We also detected significantly longer TCTs (p < 0.05) postoperatively in the ipsilateral upper extremity. This study suggests a long-term worsening of fine motor skills even three months after SMA tumor resection, indicating the necessity of targeted physical therapy for these patients.

Evaluating a cutting-edge augmented reality-supported navigation system for spinal instrumentation.

OBJECTIVE: Dorsal instrumentation using pedicle screws is a standard treatment for multiple spinal pathologies, such as trauma, infection, or degenerative indications. Intraoperative three-dimensional (3D) imaging and navigated pedicle screw placement are used at multiple centers. For the present study, we evaluated a new navigation system enabling augmented reality (AR)-supported pedicle screw placement while integrating navigation cameras into the reference array and drill guide. The present study aimed to evaluate its clinical application regarding safety, efficacy, and accuracy. METHODS: A total of 20 patients were operated on between 06/2021 and 01/2022 using the new technique for intraoperative navigation. Intraoperative data with a focus on accuracy and patient safety, including patient outcome, were analyzed. The accuracy of pedicle screw placement was evaluated by intraoperative CT imaging. RESULTS: A median of 8 (4-18) pedicle screws were placed in each case. Percutaneous instrumentation was performed in 14 patients (70%). The duration of pedicle screw placement (duration scan-scan) was 56 ± 26 (30-107) min. Intraoperative screw revision was necessary for 3 of 180 pedicle screws (1.7%). Intraoperatively, no major complications occurred-one case of delay due to software issues and one case of difficult screw placement were reported. CONCLUSION: The current study's results could confirm the use of the present AR-supported system for navigated pedicle screw placement for dorsal instrumentation in clinical routine. It provides a reliable and safe tool for 3D imaging-based pedicle screw placement, only requires a minimal intraoperative setup, and provides new opportunities by integrating AR.

Balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension: a clinical consensus statement of the ESC working group on pulmonary circulation and right ventricular function.

The current treatment algorithm for chronic thromboembolic pulmonary hypertension (CTEPH) as depicted in the 2022 European Society of Cardiology (ESC)/European Respiratory Society (ERS) guidelines on the diagnosis and treatment of pulmonary hypertension (PH) includes a multimodal approach of combinations of pulmonary endarterectomy (PEA), balloon pulmonary angioplasty (BPA) and medical therapies to target major vessel pulmonary vascular lesions, and microvasculopathy. Today, BPA of >1700 patients has been reported in the literature from centers in Asia, the US, and also Europe; many more patients have been treated outside literature reports. As BPA becomes part of routine care of patients with CTEPH, benchmarks for safe and effective care delivery become increasingly important. In light of this development, the ESC Working Group on Pulmonary Circulation and Right Ventricular Function has decided to publish a document that helps standardize BPA to meet the need of uniformity in patient selection, procedural planning, technical approach, materials and devices, treatment goals, complications including their management, and patient follow-up, thus complementing the guidelines. Delphi methodology was utilized for statements that were not evidence based. First, an anatomical nomenclature and a description of vascular lesions are provided. Second, treatment goals and definitions of complete BPA are outlined. Third, definitions of complications are presented which may be the basis for a standardized reporting in studies involving BPA. The document is intended to serve as a companion to the official ESC/ERS guidelines.

Hypofractionated stereotactic radiotherapy (HFSRT) versus single fraction stereotactic radiosurgery (SRS) to the resection cavity of brain metastases after surgical resection (SATURNUS): study protocol for a randomized phase III trial.

BACKGROUND: The brain is a common site for cancer metastases. In case of large and/or symptomatic brain metastases, neurosurgical resection is performed. Adjuvant radiotherapy is a standard procedure to minimize the risk of local recurrence and is increasingly performed as local stereotactic radiotherapy to the resection cavity. Both hypofractionated stereotactic radiotherapy (HFSRT) and single fraction stereotactic radiosurgery (SRS) can be applied in this case. Although adjuvant stereotactic radiotherapy to the resection cavity is widely used in clinical routine and recommended in international guidelines, the optimal fractionation scheme still remains unclear. The SATURNUS trial prospectively compares adjuvant HFSRT with SRS and seeks to detect the superiority of HFSRT over SRS in terms of local tumor control. METHODS: In this single center two-armed randomized phase III trial, adjuvant radiotherapy to the resection cavity of brain metastases with HFSRT (6 - 7 × 5 Gy prescribed to the surrounding isodose) is compared to SRS (1 × 12-20 Gy prescribed to the surrounding isodose). Patients are randomized 1:1 into the two different treatment arms. The primary endpoint of the trial is local control at the resected site at 12 months. The trial is based on the hypothesis that HFSRT is superior to SRS in terms of local tumor control. DISCUSSION: Although adjuvant stereotactic radiotherapy after resection of brain metastases is considered standard of care treatment, there is a need for further prospective research to determine the optimal fractionation scheme. To the best of our knowledge, the SATURNUS study is the only randomized phase III study comparing different regimes of postoperative stereotactic radiotherapy to the resection cavity adequately powered to detect the superiority of HFSRT regarding local control. TRIAL REGISTRATION: The study was retrospectively registered with ClinicalTrials.gov, number NCT05160818, on December 16, 2021. The trial registry record is available on  https://clinicaltrials.gov/study/NCT05160818 . The presented protocol refers to version V1.3 from March 21, 2021.

Preoperative angiographic considerations and neurological outcome after surgical treatment of intradural spinal hemangioblastoma: a multicenter retrospective case series.

PURPOSE: Intradural spinal hemangioblastomas are rare highly hypervascularized benign neoplasms. Surgical resection remains the treatment of choice, with a significant risk of postoperative neurological deterioration. Due to the tumor infrequency, scientific evidence is scarce and limited to case reports and small case series. METHODS: We performed a retrospective multicenter study including five high-volume neurosurgical centers analyzing patients surgically treated for spinal hemangioblastomas between 2006 and 2021. We assessed clinical status, surgical data, preoperative angiograms, and embolization when available. Follow-up records were analyzed, and logistic regression performed to assess possible risk factors for neurological deterioration. RESULTS: We included 60 patients in Germany and Austria. Preoperative angiography was performed in 30% of the cases; 10% of the patients underwent preoperative embolization. Posterior tumor location and presence of a syrinx favored gross total tumor resection (93.8% vs. 83.3% and 97.1% vs. 84%). Preoperative embolization was not associated with postoperative worsening. The clinical outcome revealed a transient postoperative neurological deterioration in 38.3%, depending on symptom duration and preoperative modified McCormick grading, but patients recovered in most cases until follow-up. CONCLUSION: Spinal hemangioblastoma patients significantly benefit from early surgical treatment with only transient postoperative deterioration and complete recovery until follow-up. The performance of preoperative angiograms remains subject to center disparities.

Fully Integrated Laser Guidance for CT-Based Punctures: A Study in Phantoms and Patients.

PURPOSE: To test the hypothesis of equal or even superior applicability and accuracy of a fully integrated, laser-based computed tomography (CT) navigation system compared with conventional CT guidance for percutaneous interventions. MATERIALS AND METHODS: CT-guided punctures were first performed in phantoms. Four radiologists with different experience levels (2 residents (L.B., C.D.) and 2 board-certified radiologists (B.M., K.R.) performed 48 punctures using both conventional image-guided and laser-guided approaches. Subsequently, 12 punctures were performed in patients during a clinical pilot trial. Phantom targets required an in-plane or a single-/double-angulated, out-of-plane approach. Planning and intervention time, control scan number, radiation exposure, and accuracy of needle placement (measured by deviation of the needle tip to the designated target) were assessed for each guidance technique and compared (Mann-Whitney U test and t test). Patient interventions were additionally analyzed for applicability in a clinical setting. RESULTS: The application of laser guidance software in the phantom study and in 12 human patients in a clinical setting was both technically and clinically feasible in all cases. The mean planning time (P = .009), intervention time (P = .005), control scan number (P < .001), and radiation exposure (P = .013) significantly decreased for laser-navigated punctures compared with those for conventional CT guidance and especially in punctures with out-of-plane-trajectories. The accuracy significantly increased for laser-guided interventions compared with that for conventional CT (P < .001). CONCLUSIONS: Interventional radiologists with differing levels of experience performed faster and more accurate punctures for out-of-plane trajectories in the phantom models, using a new, fully integrated, laser-guided CT software and demonstrated excellent clinical and technical success in initial clinical experiments.

A rare case of H3K27-altered diffuse midline glioma with multiple osseous and spinal metastases at the time of diagnosis.

BACKGROUND: H3K27-altered diffuse midline gliomas are uncommon central nervous system tumors with extremely poor prognoses. CASE PRESENTATION: We report the case of a 24-year-old man patient with multiple, inter alia osseous metastases who presented with back pain, hemi-hypoesthesia, and hemi-hyperhidrosis. The patient underwent combined radio-chemotherapy and demonstrated temporary improvement before deteriorating. CONCLUSIONS: H3K27-altered diffuse midline glioma presents an infrequent but crucial differential diagnosis and should be considered in cases with rapid neurological deterioration and multiple intracranial and intramedullary tumor lesions in children and young adults. Combined radio-chemotherapy delayed the neurological deterioration, but unfortunately, progression occurred three months after the diagnosis.

Association of immature platelets with perioperative complications in neurosurgery.

Immature platelets are newly formed platelets with an increased prothrombotic potential. This study evaluates whether immature platelets are associated with relevant complications in neurosurgical patients. Data were obtained in the frame of a prospectively conducted observational study exploring the association between immature platelets and major cardiovascular events after surgery. Immature platelet fraction (IPF) and H-IPF (highly fluorescent immature platelet fraction) were measured preoperatively and postoperatively at the neurosurgical ward (24-72 hours after surgery). Therapy-relevant complications after surgery were stratified using the Clavien-Dindo Grade (CDG >2) as primary outcome. Data were analyzed in 391 neurosurgical patients. While preoperatively there were no differences in IPF or H-IPF, patients with higher therapy-complication grades had higher values post-op compared to patients with lower grade complications (≤2 CDG). Cut-off values identified by receiver operating characteristic curve analysis revealed that there were significantly more patients with H-IPF ≥0.95% in the group with serious complications (CDG >2) [odds ratio OR (95% confidence interval CI) = 2.06 (1.09-3.9), p = .025], whereas this association was not present for the IPF cutoff value. In a multivariate model, H-IPF≥0.95% was independently associated with serious complications after surgery [OR (95% CI) = 1.97 (1.03-3.78), p = .041]. These findings suggest that H-IPF is associated with surgical complications and may improve risk stratification of neurosurgical patients (clinicaltrials.gov: NCT02097602, registration date: 27/03/2014).

What is the context?Immature platelets are newly formed platelets with a higher thrombotic potential and play an important role in atherothrombotic events.Higher levels of immature platelets were observed in patients with acute coronary syndrome or stroke.Lately, the focus in immature platelet research shifted from observation to outcomes. Immature platelets were identified as independent predictors of major cardiovascular events in cardiologic patients with coronary artery disease. Besides, an association between immature platelets and major cardiovascular events was described in surgical patients after non-cardiac surgery.What is new?This study builds on these findings and extends the focus to perioperative complications after neurosurgery.The data were obtained prospectively in the frame of an observational clinical trial exploring the association of immature platelets and major cardiovascular events in general. Data measured in the neurosurgical cohort of that study (391 neurosurgical patients) were analyzed in the present work.Within the limitations of our study, our analyses suggest that the postoperative IPF (immature platelet fraction) and H-IPF (highly fluorescent immature platelet fraction) values, which were measured at the neurosurgical ward after surgery are both associated with higher therapy-relevant complication grades (>2 according to Clavien-Dindo Grade), whereas preoperatively obtained values were not.What is the impact?This is the first study showing a relationship between immature platelets and therapy-relevant perioperative complications in neurosurgical patients. It could be a pilot trial for varied scientific questions including risk stratification of neurosurgical patients.

RAS-challenge as a first-look test for detection of primary aldosteronism in patients with treatment-resistant hypertension.

PURPOSE: Primary aldosteronism (PA), characterised by low-renin hypertension, confers a high cardiovascular risk and is the most common cause of secondary hypertension, with an increased prevalence in patients with treatment-resistant hypertension. However, it is estimated that only a small percentage of affected patients are identified in routine clinical practice. Inhibitors of the renin-angiotensin system cause an increase in renin levels in patients with intact aldosterone regulation, and inadequate low renin with concurrent RAS inhibition (RASi) may therefore indicate PA, which could serve as a first look screening test for selection for formal work-up. METHODS: We analysed patients between 2016-2018 with treatment-resistant hypertension who had inadequate low renin in the presence of RASi (i. e. at risk for PA) and who were offered systematic work-up with adrenal vein sampling (AVS). RESULTS: A total of 26 pts were included in the study (age 54.8 ± 11, male 65%). Mean office blood pressure (BP) was 154/95 mmHg on 4.5 antihypertensive drug classes. AVS had a high technical success rate (96%) and demonstrated unilateral disease in the majority of patients (57%), most of which (77%) were undetected by cross-sectional imaging. CONCLUSION: In patients with resistant hypertension, low renin in the presence of RASi is a strong indicator for autonomous aldosterone secretion. It may serve as an on-medication screening test for PA to select for formal PA work up.

What is the context? Primary aldosteronism (PA) is associated with an uncontrolled secretion of the hormone aldosterone and often causes severe forms of high blood pressure. PA is considered the most common cause of high blood pressure which is caused by another medical condition. Medical societies have issued precise recommendations for the screening of this disease, which includes the determination of aldosterone and its main regulator renin. However, it is estimated that only a small percentage of affected patients are identified in routine clinical practice.What is the problem? In clinical studies, the determination of renin, aldosterone and its ratio (ARR) proved to be a valid screening tool. Nevertheless, in everyday life assessing and interpreting these results can be challenging for the clinician. The ARR is influenced by all first-line antihypertensives and in case of doubt, an extensive change in medication is recommended. Especially patients with resistant hypertension may require intensive medical care when medication is changed.What is important? In this study, we analysed patients at risk for PA who had inadequate low renin in presence of RASi (ACE inhibitors, Angiotensin receptor blockers). This study suggests that in patients with severe hypertension, the determination of renin in presence of RASi can provide further information on the presence of autonomic aldosterone secretion at a glance. However, this approach cannot and should not replace the algorithm proposed by current guidelines. In contrast, this approach should be an easy-to-implement concept that should prime the initiation of further appropriate diagnostics.

Interhemispheric connections in the maintenance of language performance and prognosis prediction: fully connected layer-based deep learning model analysis.

OBJECTIVE: Language-related networks have been recognized in functional maintenance, which has also been considered the mechanism of plasticity and reorganization in patients with cerebral malignant tumors. However, the role of interhemispheric connections (ICs) in language restoration remains unclear at the network level. Navigated transcranial magnetic stimulation (nTMS) and diffusion tensor imaging fiber tracking data were used to identify language-eloquent regions and their corresponding subcortical structures, respectively. METHODS: Preoperative image-based IC networks and nTMS mapping data from 30 patients without preoperative and postoperative aphasia as the nonaphasia group, 30 patients with preoperative and postoperative aphasia as the glioma-induced aphasia (GIA) group, and 30 patients without preoperative aphasia but who developed aphasia after the operation as the surgery-related aphasia group were investigated using fully connected layer-based deep learning (FC-DL) analysis to weight ICs. RESULTS: GIA patients had more weighted ICs than the patients in the other groups. Weighted ICs between the left precuneus and right paracentral lobule, and between the left and right cuneus, were significantly different among these three groups. The FC-DL approach for modeling functional and structural connectivity was also tested for its potential to predict postoperative language levels, and both the achieved sensitivity and specificity were greater than 70%. Weighted IC was reorganized more in GIA patients to compensate for language loss. CONCLUSIONS: The authors' method offers a new perspective to investigate brain structural organization and predict functional prognosis.

Neurocognitive monitoring in patients undergoing opioid pain medication after spinal surgery: a feasibility study of a new monitoring method.

PURPOSE: Patients undergoing spinal surgery require postoperative pain management to alleviate wound pain. Pain medication includes WHO grade 1 analgesic as well as potent opioids, potentially leading to cognitive decline. Up until now, the cognitive impairment is only poorly studied and difficult to monitor. We hereby investigate the feasibility of a digital monitoring method for neurocognitive function under opioid medication after spinal instrumentation. METHODS: Prospective monocenter feasibility study enrolling patients before undergoing spinal surgery. We performed cognitive testing using a tablet-based application before (baseline), as well as on day 2 after surgery (intravenous opioids), before discharge (oral opioids), and at follow-up. We recorded the exact pain medication and its other side effects. Potential risk factors for the postoperative decline in cognition included age, high-dose opioid application, and length of surgery. RESULTS: We included 20 patients in our study. The baseline assessment revealed no cognitive impairment before surgery. All patients underwent dorsal instrumentation for degenerative (60%), osteoporotic fracture (15%), or spinal tumor (25%) indications. Cognitive testing after surgery showed a significant decline under intravenous opioid therapy including short time and delayed verbal recall (p < 0.001) as well as arithmetic fluency. Cognitive performance significantly improved with partial recovery until follow-up and opioid discontinuation. CONCLUSION: Cognition testing and monitoring of neurocognitive decline under high-dose opioid medication were feasible using the digital tablet-based application. The cognition app helps to identify difficulties in cognitive function as a side effect of overdosage in opioid medication, and care givers should evaluate the risk of non-comprehension and impaired informed consent appropriately.