Deep-learning-based reconstruction of undersampled MRI to reduce scan times: a multicentre, retrospective, cohort study.

BACKGROUND: The extended acquisition times required for MRI limit its availability in resource-constrained settings. Consequently, accelerating MRI by undersampling k-space data, which is necessary to reconstruct an image, has been a long-standing but important challenge. We aimed to develop a deep convolutional neural network (dCNN) optimisation method for MRI reconstruction and to reduce scan times and evaluate its effect on image quality and accuracy of oncological imaging biomarkers. METHODS: In this multicentre, retrospective, cohort study, MRI data from patients with glioblastoma treated at Heidelberg University Hospital (775 patients and 775 examinations) and from the phase 2 CORE trial (260 patients, 1083 examinations, and 58 institutions) and the phase 3 CENTRIC trial (505 patients, 3147 examinations, and 139 institutions) were used to develop, train, and test dCNN for reconstructing MRI from highly undersampled single-coil k-space data with various acceleration rates (R=2, 4, 6, 8, 10, and 15). Independent testing was performed with MRIs from the phase 2/3 EORTC-26101 trial (528 patients with glioblastoma, 1974 examinations, and 32 institutions). The similarity between undersampled dCNN-reconstructed and original MRIs was quantified with various image quality metrics, including structural similarity index measure (SSIM) and the accuracy of undersampled dCNN-reconstructed MRI on downstream radiological assessment of imaging biomarkers in oncology (automated artificial intelligence-based quantification of tumour burden and treatment response) was performed in the EORTC-26101 test dataset. The public NYU Langone Health fastMRI brain test dataset (558 patients and 558 examinations) was used to validate the generalisability and robustness of the dCNN for reconstructing MRIs from available multi-coil (parallel imaging) k-space data. FINDINGS: In the EORTC-26101 test dataset, the median SSIM of undersampled dCNN-reconstructed MRI ranged from 0·88 to 0·99 across different acceleration rates, with 0·92 (95% CI 0·92-0·93) for 10-times acceleration (R=10). The 10-times undersampled dCNN-reconstructed MRI yielded excellent agreement with original MRI when assessing volumes of contrast-enhancing tumour (median DICE for spatial agreement of 0·89 [95% CI 0·88 to 0·89]; median volume difference of 0·01 cm3 [95% CI 0·00 to 0·03] equalling 0·21%; p=0·0036 for equivalence) or non-enhancing tumour or oedema (median DICE of 0·94 [95% CI 0·94 to 0·95]; median volume difference of -0·79 cm3 [95% CI -0·87 to -0·72] equalling -1·77%; p=0·023 for equivalence) in the EORTC-26101 test dataset. Automated volumetric tumour response assessment in the EORTC-26101 test dataset yielded an identical median time to progression of 4·27 months (95% CI 4·14 to 4·57) when using 10-times-undersampled dCNN-reconstructed or original MRI (log-rank p=0·80) and agreement in the time to progression in 374 (95·2%) of 393 patients with data. The dCNN generalised well to the fastMRI brain dataset, with significant improvements in the median SSIM when using multi-coil compared with single-coil k-space data (p<0·0001). INTERPRETATION: Deep-learning-based reconstruction of undersampled MRI allows for a substantial reduction of scan times, with a 10-times acceleration demonstrating excellent image quality while preserving the accuracy of derived imaging biomarkers for the assessment of oncological treatment response. Our developments are available as open source software and hold considerable promise for increasing the accessibility to MRI, pending further prospective validation. FUNDING: Deutsche Forschungsgemeinschaft (German Research Foundation) and an Else Kröner Clinician Scientist Endowed Professorship by the Else Kröner Fresenius Foundation.

[Focusing on intersectorality-strategies and current research projects for the care of geriatric people]. / Intersektoralität im Fokus ­ Strategien und aktuelle Forschungsprojekte zur Versorgung geriatrischer Personen.

In view of the demographic change, the need for intersectoral care of the aging population has already been identified. The strategies for implementation are diverse and address different approaches, each of which requires different sectors to overlap. This article provides an overview of already completed and ongoing projects for the care of geriatric patients. It becomes apparent that the development of networks as an indispensable basis for intersectoral care cannot be measured in terms of direct intervention effects and therefore makes it difficult to prove the cost-benefit. It is also evident that some research projects fail to be implemented into standard care due to financial and staff shortages.Do we need a rethinking in Germany or less innovation-related funding lines for better implementation and research of existing concepts? International role models such as Japan show that cost reduction for the care of the aging population should be considered in the long term, which requires increased financial volumes in the short term. For a sustainable implementation of cross-sectoral approaches into everyday life, research should therefore reorganize tight and/or entrenched structures, processes, and financing. By linking the countless existing projects and integrating ideas from different sectors, future demands of intersectoral geriatric care may be achieved.

[Evidence-based inpatient psychotherapy in borderline personality disorder]. / Evidenzbasierte stationäre Psychotherapie der Borderline-Persönlichkeitsstörung.

BACKGROUND: Borderline personality disorder (BPD) is frequent (prevalence in Germany between 0.7% and 4.5%) [11] and is associated with a high level of psychological stress and frequent emergency inpatient admissions. The provision of disorder-specific outpatient psychotherapy is still insufficient also in Germany. OBJECTIVE: This article provides an overview of the available data on the effectiveness of inpatient psychotherapy for BPD. MATERIAL AND METHODS: A qualitative review on the effectiveness and therapy outcome predictors was conducted based on a literature search in PubMed. RESULTS: Overall, very few randomized controlled trials are available; in contrast uncontrolled studies are predominant. Most evidence is available for dialectical behavior therapy (DBT) but other approaches, including psychodynamic procedures, have also been studied. DISCUSSION: The currently available data suggest an efficacy of inpatient psychotherapy for BPD; however, randomized trials with larger samples and sufficient representation including male patients are largely lacking. There is also no substantial direct evidence for the superiority of inpatient compared to outpatient psychotherapy.

Implementation of TERT promoter mutations improve prognostication of the WHO classification in meningioma.

TERT promoter mutations have been associated with increased risk of recurrence in meningioma cohorts, thus a potential biomarker for aggressive phenotypes. A main purpose of refining tumour classification is better predictions on the patient level. We compiled data from previous published cohorts to investigate patient-level predictions of recurrence based on TERTp-mut status. Implementation of TERTp-mut into the WHO grading led to better patient prognostication by improved prediction of recurrence. Our results support implementation of TERTp-mut into diagnostics and classification of meningiomas.

Novel insights into pivotal risk factors for rectal carriage of extended-spectrum-ß-lactamase-producing enterobacterales within the general population in Lower Saxony, Germany.

AIMS: To estimate the prevalence of extended-spectrum-ß-lactamase (ESBL)-producing enterobacterales (ESBL-E) carriage in the general population of Lower Saxony, Germany, and to identify risk factors for being colonized. METHODS AND RESULTS: Participants were recruited through local press and information events. Detection of ESBL-E by culture was conducted using ESBL-selective chromagar plates containing third-generation cephalosporins. Identification of pathogens was performed using matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF)_technology on Vitek mass spectrometry. Antibiotic susceptibility testing was conducted by microdilution (Vitek II) and an ESBL confirmation assay was carried out using a combination disk test. Of 527 randomly collected stool samples from healthy volunteers, 5.5% were tested positive for ESBL-E. Post-stratification for age and gender yielded a similar population estimate (5.9%). People traveling abroad and taking antibiotics had the greatest rectal ESBL-E carriage. CONCLUSIONS: Potential risk factors (eg, working in healthcare facilities, recent inpatient stay) did not attribute to rectal ESBL-E carriage as other factors (eg, travelling, taking antibiotics). Rectal ESBL-E carriage within the general population seems to be high. SIGNIFICANCE AND IMPACT OF THE STUDY: The known risk factors for carriage with MDRO might not be fully applicable to ESBL-E and require further examination in order to develop effective strategies for the prevention of ESBL-E dissemination within the general population.

[Structure and Organization of an Emergency Department]. / Struktur und Organisation einer zentralen Notaufnahme.

The more diverse the German hospital landscape, the more important it is to define tasks and processes in order to ensure a uniform standard of care at the highest level for the population. With the introduction of additional training in clinical acute and emergency medicine and specifications for inpatient emergency care, important foundations for the necessary structure of emergency rooms have been given.

MGMT promoter methylation analysis for allocating combined CCNU/TMZ chemotherapy: Lessons learned from the CeTeG/NOA-09 trial.

The CeTeG/NOA-09 trial showed a survival benefit for combined CCNU/TMZ therapy in MGMT-promoter-methylated glioblastoma patients (quantitative methylation-specific PCR [qMSP] ratio > 2). Here, we report on the prognostic value of the MGMT promoter methylation ratio determined by qMSP and evaluate the concordance of MGMT methylation results obtained by qMSP, pyrosequencing (PSQ) or DNA methylation arrays (MGMT-STP27). A potential association of qMSP ratio with survival was analyzed in the CeTeG/NOA-09 trial population (n = 129; log-rank tests, Cox regression analyses). The concordance of MGMT methylation assays (qMSP, PSQ and MGMT-STP27) was evaluated in 76 screened patients. Patients with tumors of qMSP ratio > 4 showed superior survival compared to those with ratios 2-4 (P = .0251, log-rank test). In multivariate analysis, the qMSP ratio was not prognostic across the study cohort (hazard ratio [HR] = 0.88; 95% CI: 0.72-1.08). With different cutoffs for qMSP ratio (4, 9, 12 or 25), the CCNU/TMZ benefit tended to be larger in subgroups with lower ratios (eg, for cutoff 9: HR 0.32 for lower subgroup, 0.73 for higher subgroup). The concordance rates with qMSP were 94.4% (PSQ) and 90.2% (MGMT-STP27). Discordant results were restricted to tumors with qMSP ratios ≤4 and PSQ mean methylation rate ≤25%. Despite a shorter survival in MGMT-promoter-methylated patients with lower methylation according to qMSP, these patients had a benefit from combined CCNU/TMZ therapy, which even tended to be stronger than in patients with higher methylation rates. With acceptable concordance rates, decisions on CCNU/TMZ therapy may also be based on PSQ or MGMT-STP27.

Prediction of TERTp-mutation status in IDH-wildtype high-grade gliomas using pre-treatment dynamic [18F]FET PET radiomics.

PURPOSE: To evaluate radiomic features extracted from standard static images (20-40 min p.i.), early summation images (5-15 min p.i.), and dynamic [18F]FET PET images for the prediction of TERTp-mutation status in patients with IDH-wildtype high-grade glioma. METHODS: A total of 159 patients (median age 60.2 years, range 19-82 years) with newly diagnosed IDH-wildtype diffuse astrocytic glioma (WHO grade III or IV) and dynamic [18F]FET PET prior to surgical intervention were enrolled and divided into a training (n = 112) and a testing cohort (n = 47) randomly. First-order, shape, and texture radiomic features were extracted from standard static (20-40 min summation images; TBR20-40), early static (5-15 min summation images; TBR5-15), and dynamic (time-to-peak; TTP) images, respectively. Recursive feature elimination was used for feature selection by 10-fold cross-validation in the training cohort after normalization, and logistic regression models were generated using the radiomic features extracted from each image to differentiate TERTp-mutation status. The areas under the ROC curve (AUC), accuracy, sensitivity, specificity, and positive and negative predictive value were calculated to illustrate diagnostic power in both the training and testing cohort. RESULTS: The TTP model comprised nine selected features and achieved highest predictability of TERTp-mutation with an AUC of 0.82 (95% confidence interval 0.71-0.92) and sensitivity of 92.1% in the independent testing cohort. Weak predictive capability was obtained in the TBR5-15 model, with an AUC of 0.61 (95% CI 0.42-0.80) in the testing cohort, while no predictive power was observed in the TBR20-40 model. CONCLUSIONS: Radiomics based on TTP images extracted from dynamic [18F]FET PET can predict the TERTp-mutation status of IDH-wildtype diffuse astrocytic high-grade gliomas with high accuracy preoperatively.

Detection of impending perfusion deficits by intraoperative computed tomography (iCT) in aneurysm surgery of the anterior circulation.

BACKGROUND: The aim of our study was to evaluate the additional benefit of intraoperative computed tomography (iCT), intraoperative computed tomography angiography (iCTA), and intraoperative computed tomography perfusion (iCTP) in the intraoperative detection of impending ischemia to established methods (indocyanine green videoangiography (ICGVA), microDoppler, intraoperative neuromonitoring (IONM)) for initiating timely therapeutic measures. METHODS: Patients with primary aneurysms of the anterior circulation between October 2016 and December 2019 were included. Data of iCT modalities compared to other techniques (ICGVA, microDoppler, IONM) was recorded with emphasis on resulting operative conclusions leading to inspection of clip position, repositioning, or immediate initiation of conservative treatment strategies. Additional variables analyzed included patient demographics, aneurysm-specific characteristics, and clinical outcome. RESULTS: Of 194 consecutive patients, 93 patients with 100 aneurysms received iCT imaging. While IONM and ICGVA were normal, an altered vessel patency in iCTA was detected in 5 (5.4%) and a mismatch in iCTP in 7 patients (7.5%). Repositioning was considered appropriate in 2 patients (2.2%), where immediate improvement in iCTP could be documented. In a further 5 cases (5.4%), intensified conservative therapy was immediately initiated treating the reduced CBP as clip repositioning was not considered causal. In terms of clinical outcome at last FU, mRS0 was achieved in 85 (91.4%) and mRS1-2 in 7 (7.5%) and remained mRS4 in one patient with SAH (1.1%). CONCLUSIONS: Especially iCTP can reveal signs of impending ischemia in selected cases and enable the surgeon to promptly initiate therapeutic measures such as clip repositioning or intraoperative onset of maximum conservative treatment, while established tools might fail to detect those intraoperative pathologic changes.

Past medical history of tumors other than meningioma is a negative prognostic factor for tumor recurrence in meningiomas WHO grade I.

BACKGROUND: Prognostic markers for meningioma recurrence are needed to guide patient management. Apart from rare hereditary syndromes, the impact of a previous unrelated tumor disease on meningioma recurrence has not been described before. METHODS: We retrospectively searched our database for patients with meningioma WHO grade I and complete resection provided between 2002 and 2016. Demographical, clinical, pathological, and outcome data were recorded. The following covariates were included in the statistical model: age, sex, clinical history of unrelated tumor disease, and localization (skull base vs. convexity). Particular interest was paid to the patients' past medical history. The study endpoint was date of tumor recurrence on imaging. Prognostic factors were obtained from multivariate proportional hazards models. RESULTS: Out of 976 meningioma patients diagnosed with a meningioma WHO grade I, 416 patients fulfilled our inclusion criteria. We encountered 305 women and 111 men with a median age of 57 years (range: 21-89 years). Forty-six patients suffered from a tumor other than meningioma, and no TERT mutation was detected in these patients. There were no differences between patients with and without a positive oncological history in terms of age, tumor localization, or mitotic cell count. Clinical history of prior tumors other than meningioma showed the strongest association with meningioma recurrence (p = 0.004, HR = 3.113, CI = 1.431-6.771) both on uni- and multivariate analysis. CONCLUSION: Past medical history of tumors other than meningioma might be associated with an increased risk of meningioma recurrence. A detailed pre-surgical history might help to identify patients at risk for early recurrence.

Lomustine-temozolomide combination therapy versus standard temozolomide therapy in patients with newly diagnosed glioblastoma with methylated MGMT promoter (CeTeG/NOA-09): a randomised, open-label, phase 3 trial.

BACKGROUND: There is an urgent need for more effective therapies for glioblastoma. Data from a previous unrandomised phase 2 trial suggested that lomustine-temozolomide plus radiotherapy might be superior to temozolomide chemoradiotherapy in newly diagnosed glioblastoma with methylation of the MGMT promoter. In the CeTeG/NOA-09 trial, we aimed to further investigate the effect of lomustine-temozolomide therapy in the setting of a randomised phase 3 trial. METHODS: In this open-label, randomised, phase 3 trial, we enrolled patients from 17 German university hospitals who were aged 18-70 years, with newly diagnosed glioblastoma with methylated MGMT promoter, and a Karnofsky Performance Score of 70% and higher. Patients were randomly assigned (1:1) with a predefined SAS-generated randomisation list to standard temozolomide chemoradiotherapy (75 mg/m2 per day concomitant to radiotherapy [59-60 Gy] followed by six courses of temozolomide 150-200 mg/m2 per day on the first 5 days of the 4-week course) or to up to six courses of lomustine (100 mg/m2 on day 1) plus temozolomide (100-200 mg/m2 per day on days 2-6 of the 6-week course) in addition to radiotherapy (59-60 Gy). Because of the different schedules, patients and physicians were not masked to treatment groups. The primary endpoint was overall survival in the modified intention-to-treat population, comprising all randomly assigned patients who started their allocated chemotherapy. The prespecified test for overall survival differences was a log-rank test stratified for centre and recursive partitioning analysis class. The trial is registered with ClinicalTrials.gov, number NCT01149109. FINDINGS: Between June 17, 2011, and April 8, 2014, 141 patients were randomly assigned to the treatment groups; 129 patients (63 in the temozolomide and 66 in the lomustine-temozolomide group) constituted the modified intention-to-treat population. Median overall survival was improved from 31·4 months (95% CI 27·7-47·1) with temozolomide to 48·1 months (32·6 months-not assessable) with lomustine-temozolomide (hazard ratio [HR] 0·60, 95% CI 0·35-1·03; p=0·0492 for log-rank analysis). A significant overall survival difference between groups was also found in a secondary analysis of the intention-to-treat population (n=141, HR 0·60, 95% CI 0·35-1·03; p=0·0432 for log-rank analysis). Adverse events of grade 3 or higher were observed in 32 (51%) of 63 patients in the temozolomide group and 39 (59%) of 66 patients in the lomustine-temozolomide group. There were no treatment-related deaths. INTERPRETATION: Our results suggest that lomustine-temozolomide chemotherapy might improve survival compared with temozolomide standard therapy in patients with newly diagnosed glioblastoma with methylated MGMT promoter. The findings should be interpreted with caution, owing to the small size of the trial. FUNDING: German Federal Ministry of Education and Research.

Poor prognosis associated with TERT gene alterations in meningioma is independent of the WHO classification: an individual patient data meta-analysis.

BACKGROUND: TERT gene alterations (TERT-alt) have been linked to increased risk of recurrence in meningiomas, whereas the association to mortality largely remain incompletely investigated. As incongruence between clinical course and WHO grade exists, reliable biomarkers have been sought. METHODS: We applied the Preferred Reporting Items for Systematic Review and Meta-Analyses of individual participant data Statement. We compiled data from eight studies and allocated patients to TERT-alt (n=59) or TERT promoter wild-type (TERTp-wt; n=618). We compared the two groups stratified for WHO grades as: incidence rates, survival probabilities and cumulative recurrences. We estimated the effects of WHO grade, age at diagnosis and sex as HRs. RESULTS: TERT-alt occurred in 4.7%, 7.9% and 15.4% of WHO-I/WHO-II/WHO-III meningiomas, respectively. The median recurrence-free survival was 14 months for all TERT-alt patients versus 101 months for all TERTp-wt patients. The HR for TERT-alt was 3.74 in reference to TERTp-wt. For all TERT-alt patients versus all TERTp-wt patients, the median overall survival was 58 months and 160 months, respectively. The HR for TERT-alt was 2.77 compared with TERTp-wt. TERT-alt affected prognosis independent of WHO grades. Particularly, the recurrence rate was 4.8 times higher in WHO-I/-II TERT-alt patients compared with WHO-III TERTp-wt patients. The mortality rate was 2.7 times higher in the WHO-I and WHO-II TERT-alt patients compared with WHO-III TERTp-wt patients. CONCLUSIONS: TERT-alt is an important biomarker for significantly higher risk of recurrence and death in meningiomas. TERT-alt should be managed and surveilled aggressively. We propose that TERT-alt analysis should be implemented as a routine diagnostic test in meningioma and integrated into the WHO classification. TRIAL REGISTRATION NUMBER: PROSPERO: CRD42018110566.

[Preventive Home Visits for Elderly People: A Systematic Appraisal of Current Application in Germany]. / Präventive Hausbesuche für ältere Menschen: eine systematische Bestandsaufnahme ihrer praktischen Anwendung in Deutschland.

OBJECTIVE: Preventive home visits (PHV) are a measure for promoting the health of elderly people. A study of these measures used over the past 40 years in many countries across the globe revealed a very diverse picture regarding targeted groups, applied structures and intervention contents. So far, there has been no clear evidence of their effectiveness on outcomes such as mortality, need for care, hospital or nursing home admissions. However, a steady increase in PHV programmes in Germany warrants an examination of the current national practice. MATERIAL/METHODS: PHV programmes in Germany were identified in the course of Internet-based research (January 2018) and systematically compared by means of nine criteria that were defined beforehand. RESULTS: 38 PHV programmes were included: 26 currently implemented, and 12 that have been terminated. These showed a considerable variety in terms of their programme components. Medicine-oriented and social environment-oriented programmes (n=8 vs. n=24) could be differentiated. Relevant differentiation criteria were sponsorship, profession of home visitors and intervention contents. Thus, the practice in Germany is characterised as follows: municipal sponsorship, social workers conducting home visits, and guidance by consulting services disregarding integrated case management. Programmes of this type mainly emerged only in the current decade. CONCLUSIONS: PHV for elderly people evolved from initially medicine-oriented into rather social environment-oriented programmes of municipal public service. They target elderly people with unclear need for support who, at the same time, are confronted with barriers to accessing suitable services. The anticipated main effect of PHV relates to the safeguarding of social participation. However, evidence for their effectiveness, still pending, should be made available before a broad or even legally anchored application is envisaged.

Glioblastoma Exhibits Inter-Individual Heterogeneity of TSPO and LAT1 Expression in Neoplastic and Parenchymal Cells.

Molecular imaging is essential for diagnosis and treatment planning for glioblastoma patients. Positron emission tomography (PET) with tracers for the detection of the solute carrier family 7 member 5 (SLC7A5; also known as the amino acid transporter light chain L system, LAT1) and for the mitochondrial translocator protein (TSPO) is successfully used to provide additional information on tumor volume and prognosis. The current approaches for TSPO-PET and the visualization of tracer ([18F] Fluoroethyltyrosine, FET) uptake by LAT1 (FET-PET) do not yet exploit the full diagnostic potential of these molecular imaging techniques. Therefore, we investigated the expression of TSPO and LAT1 in patient glioblastoma (GBM) samples, as well as in various GBM mouse models representing patient GBMs of different genetic subtypes. By immunohistochemistry, we found that TSPO and LAT1 are upregulated in human GBM samples compared to normal brain tissue. Next, we orthotopically implanted patient-derived GBM cells, as well as genetically engineered murine GBM cells, representing different genetic subtypes of the disease. To determine TSPO and LAT1 expression, we performed immunofluorescence staining. We found that both TSPO and LAT1 expression was increased in tumor regions of the implanted human or murine GBM cells when compared to the neighboring mouse brain tissue. While LAT1 was largely restricted to tumor cells, we found that TSPO was also expressed by microglia, tumor-associated macrophages, endothelial cells, and pericytes. The Cancer Genome Atlas (TCGA)-data analysis corroborates the upregulation of TSPO in a bigger cohort of GBM patient samples compared to tumor-free brain tissue. In addition, AIF1 (the gene encoding for the myeloid cell marker Iba1) was also upregulated in GBM compared to the control. Interestingly, TSPO, as well as AIF1, showed significantly different expression levels depending on the GBM genetic subtype, with the highest expression being exhibited in the mesenchymal subtype. High TSPO and AIF1 expression also correlated with a significant decrease in patient survival compared to low expression. In line with this finding, the expression levels for TSPO and AIF1 were also significantly higher in (isocitrate-dehydrogenase wild-type) IDHWT compared to IDH mutant (IDHMUT) GBM. LAT1 expression, on the other hand, was not different among the individual GBM subtypes. Therefore, we could conclude that FET- and TSPO-PET confer different information on pathological features based on different genetic GBM subtypes and may thus help in planning individualized strategies for brain tumor therapy in the future. A combination of TSPO-PET and FET-PET could be a promising way to visualize tumor-associated myeloid cells and select patients for treatment strategies targeting the myeloid compartment.

Non-invasive prediction of IDH-wildtype genotype in gliomas using dynamic 18F-FET PET.

PURPOSE: According to the updated WHO classification of gliomas with its emphasis on molecular parameters, tumours with an IDH-wildtype status have a dismal prognosis. To ensure timely adjustment of treatment, demand for non-invasive prediction methods is high. 18F-FET PET has been shown to be an important diagnostic tool for glioma management. The aim of this study was to assess the value of dynamic 18F-FET PET for the non-invasive prediction of the IDH-mutation status. METHODS: Newly diagnosed WHO grade II-IV glioma patients with MRI and dynamic 18F-FET PET were included. The 18F-FET PET parameters mean and maximal tumour-to-background ratio (TBRmean, TBRmax) and minimal time-to-peak (TTPmin) were evaluated. The diagnostic power for the prediction of the IDH genotype (positive/negative predictive value) was tested in the overall study group and in the subgroup of non-contrast enhancing gliomas. RESULTS: Three hundred forty-one patients were evaluated. Molecular analyses revealed 178 IDH-mutant and 163 IDH-wildtype tumours. Overall, 270/341 gliomas were classified as 18F-FET-positive (TBRmax > 1.6), 90.2% of the IDH-wildtype and 69.1% of IDH-mutant gliomas. Median TBRmax was significantly higher in IDH-wildtype compared with IDH-mutant gliomas (2.9 vs. 2.3, p < 0.001); however, ROC-analyses revealed no reliable cutoff due to a high overlap (range 1.0-7.1 vs. 1.1-7.9). Dynamic analysis revealed a significantly shorter TTPmin in IDH-wildtype gliomas; using TTPmin ≤ 12.5 min as indicator for IDH-wildtype gliomas, a positive predictive value of 87% was reached (negative predictive value 72%, AUC = 0.796, p ≤ 0.001). A total of 161/341 gliomas did not show contrast enhancement on MRI; even within this subgroup, TTPmin ≤ 12.5 min remained a good predictor of IDH-wildtype glioma (positive predictive value 83%, negative predictive value 90%; AUC = 0.868, p < 0.001). CONCLUSION: A short TTPmin in dynamic 18F-FET PET serves as good predictor of highly aggressive IDH-wildtype status in gliomas. In particular, a high diagnostic power was observed in the subgroup of non-contrast enhancing gliomas, which helps to identify patients with worse prognosis.

Joint EANM/EANO/RANO practice guidelines/SNMMI procedure standards for imaging of gliomas using PET with radiolabelled amino acids and [18F]FDG: version 1.0.

These joint practice guidelines, or procedure standards, were developed collaboratively by the European Association of Nuclear Medicine (EANM), the Society of Nuclear Medicine and Molecular Imaging (SNMMI), the European Association of Neurooncology (EANO), and the working group for Response Assessment in Neurooncology with PET (PET-RANO). Brain PET imaging is being increasingly used to supplement MRI in the clinical management of glioma. The aim of these standards/guidelines is to assist nuclear medicine practitioners in recommending, performing, interpreting and reporting the results of brain PET imaging in patients with glioma to achieve a high-quality imaging standard for PET using FDG and the radiolabelled amino acids MET, FET and FDOPA. This will help promote the appropriate use of PET imaging and contribute to evidence-based medicine that may improve the diagnostic impact of this technique in neurooncological practice. The present document replaces a former version of the guidelines published in 2006 (Vander Borght et al. Eur J Nucl Med Mol Imaging. 33:1374-80, 2006), and supplements a recent evidence-based recommendation by the PET-RANO working group and EANO on the clinical use of PET imaging in patients with glioma (Albert et al. Neuro Oncol. 18:1199-208, 2016). The information provided should be taken in the context of local conditions and regulations.

Significance of cerebrospinal fluid inflammatory markers for diagnosing external ventricular drain-associated ventriculitis in patients with severe traumatic brain injury.

Objective: The aim of this study was to investigate the diagnostic potential of the inflammatory markers interleukin-6 (IL-6), total leukocyte count (TLC), and protein in the CSF and IL-6, C-reactive protein, and white blood cell count in the serum for the early diagnosis of ventriculitis in patients with traumatic brain injury (TBI) and an external ventricular drain compared with patients without ventriculitis. Methods: Retrospective data from 40 consecutive patients with TBI and an external ventricular drain treated in the authors' intensive care unit between 2013 and 2017 were analyzed. For all markers, arithmetical means and standard deviations, area under the curve (AUC), cutoff values, sensitivity, specificity, positive likelihood ratio (LR), and negative LR were calculated and correlated with presence or absence of ventriculitis. Results: There were 35 patients without ventriculitis and 5 patients with ventriculitis. The mean ± SD IL-6 concentration in CSF was significantly increased, with 6519 ± 4268 pg/mL at onset of ventriculitis compared with 1065 ± 1705 pg/mL in patients without ventriculitis (p = 0.04). Regarding inflammatory markers in CSF, IL-6 showed the highest diagnostic potential for differentiation between the presence and absence of ventriculitis (AUC 0.938, cutoff 4064 pg/mL, sensitivity 100%, specificity 92.3%, positive LR 13, and negative LR 0), followed by TLC (AUC 0.900, cutoff 64.5 /µL, sensitivity 100%, specificity 80%, positive LR 5.0, and negative LR 0) and protein (AUC 0.876, cutoff 31.5 mg/dL, sensitivity 100%, specificity 62.5%, positive LR 2.7, and negative LR 0). Conclusions: The level of IL-6 in CSF has the highest diagnostic value of all investigated inflammatory markers for detecting ventriculitis in TBI patients at an early stage. In particular, CSF IL-6 levels higher than the threshold of 4064 pg/mL were significantly associated with the probability of ventriculitis.

Utilization, Safety, and Technical Performance of a Telemedicine System for Prehospital Emergency Care: Observational Study.

BACKGROUND: As a consequence of increasing emergency medical service (EMS) missions requiring an EMS physician on site, we had implemented a unique prehospital telemedical emergency service as a new structural component to the conventional physician-based EMS in Germany. OBJECTIVE: We sought to assess the utilization, safety, and technical performance of this telemedical emergency service. METHODS: We conducted a retrospective analysis of all primary emergency missions with telemedical consultation of an EMS physician in the City of Aachen (250,000 inhabitants) during the first 3 operational years of our tele-EMS system. Main outcome measures were the number of teleconsultations, number of complications, and number of transmission malfunctions during teleconsultations. RESULTS: The data of 6265 patients were analyzed. The number of teleconsultations increased during the run-in period of four quarters toward full routine operation from 152 to 420 missions per quarter. When fully operational, around the clock, and providing teleconsultations to 11 mobile ambulances, the number of teleconsultations further increased by 25.9 per quarter (95% CI 9.1-42.6; P=.009). Only 6 of 6265 patients (0.10%; 95% CI 0.04%-0.21%) experienced adverse events, all of them not inherent in the system of teleconsultations. Technical malfunctions of single transmission components occurred from as low as 0.3% (95% CI 0.2%-0.5%) during two-way voice communications to as high as 1.9% (95% CI 1.6%-2.3%) during real-time vital data transmissions. Complete system failures occurred in only 0.3% (95% CI 0.2%-0.6%) of all teleconsultations. CONCLUSIONS: The Aachen prehospital EMS is a frequently used, safe, and technically reliable system to provide medical care for emergency patients without an EMS physician physically present. Noninferiority of the tele-EMS physician compared with an on-site EMS physician needs to be demonstrated in a randomized trial.

Role of amino-tracer PET for decision-making in neuro-oncology.

PURPOSE OF REVIEW: To give an overview on the current development in PET imaging as an additional tool in brain tumor management. RECENT FINDINGS: The rising emphasis on molecular tumor characteristics both in primary and in metastatic brain disease leads to an increased demand for noninvasive 'molecular' grading as well as treatment planning and surveillance of therapy effects. Metabolic imaging using amino acid PET provides further insights into tumor metabolism; current novelties comprise the use of hybrid PET/MRI scanners as well as development of new tracers. Furthermore, treatment monitoring and prognostication on the basis of amino acid PET is gaining further importance in neuro-oncological decision-making. SUMMARY: Due to its unique properties in visualization of tumor biology, amino acid PET will continue to gain further importance in primary and secondary brain tumors.

18F-FET-PET as a biomarker for therapy response in non-contrast enhancing glioma following chemotherapy.

BACKGROUND: Monitoring treatment response after chemotherapy of gadolinium-(Gd)-negative gliomas is challenging as conventional MRI often indicates no radiological changes. We hypothesize that 18F-FET-PET can be used as a biomarker for response assessment in Gd-negative gliomas undergoing chemotherapy. METHODS: Sixty-one patients harboring Gd-negative WHO grade II or III glioma receiving alkylating agents (temozolomide or CCNU/procarbacine) were included. All patients underwent MRI and 18F-FET-PET before chemotherapy and 6 months later. We calculated T2-volume, 18F-FET-PET based biological tumour volume (BTV) and maximal tumour-to-brain ratio (TBRmax). Moreover, dynamic PET acquisition was performed using time-activity-curves (TACs) analysis. For MRI-based response assessment, RANO criteria for low-grade glioma were used. For 18F-FET-PET, following classification scheme was tested: responsive disease (RD) when a decrease in either BTV ≥ 25% and/or TBRmax ≥ 10% occurred, an increase in BTV ≥ 25% and/or TBRmax increase > 10% characterized progressive disease (PD), minor changes ± 25% for BTV and ± 10% for TBRmax were regarded as stable disease (SD). Post-chemotherapy survival (PCS) and time-to-treatment failure (TTF) were calculated using the Kaplan-Meier method. RESULTS: 18F-FET-PET based response has shown patients with RD to have the longest TTF time (78.5 vs 24.6 vs 24.1 months, p = 0.001), while there was no significant difference between patients with a SD and PD. A comparable pattern was observed for PCS (p < 0.001). T2-volume based assessment was not associated with outcome. CONCLUSION: 18F-FET-PET is a promising biomarker for early response assessment in Gd-negative gliomas undergoing chemotherapy. It might be helpful for a timely adjustment of potentially ineffective treatment concepts and overcomes limitations of conventional structural imaging.