In-patient neurosurgical tumor treatments for malignant glioma patients in Germany.

OBJECTIVE: Treatment for malignant gliomas involves multiple disciplines, including neurosurgery, radiation therapy, medical and neuro-oncology, and palliative medicine, with function-preserving neurosurgical tumor removal being crucial. However, real-world data on hospital cases, treatment types, especially regarding surgical approaches, and the associated complication and mortality rates in Germany are lacking. METHODS: We analyzed data on hospital cases involving malignant gliomas (ICD-10-GM code C71) from the German §21 Hospital Remuneration Act, provided by the Institute for the Hospital Remuneration System (InEK GmbH), from 2019 to 2022. Our focus was on neuro-oncological operations defined by the German Cancer Society (DKG) and included specific operation and procedure (OPS) codes. RESULTS: From 2019 to 2022, there were 101,192 hospital cases involving malignant gliomas in Germany. Neurosurgical tumor removal was performed in 27,193 cases (26.9%). Microsurgical techniques were used in 95% of surgeries, intraoperative navigation systems in 84%, fluorescence-guided surgeries in 45.6%, and intraoperative neurophysiological monitoring (IONM) in 46.4%. Surgical or medical complications occurred in 2903 cases (10.7%). The hospital mortality rate was 2.7%. Mortality was significantly higher in patients aged 65 and older (Odds ratio 2.9, p < 0.0001), and lower in cases using fluorescence-guided procedures (Odds ratio 0.8, p = 0.015) and IONM (Odds ratio 0.5, p < 0.0001). CONCLUSIONS: Over the course of 4 years, over 100,000 hospital cases involving adult patients diagnosed with malignant gliomas were treated in Germany, with 27,193 cases undergoing tumor removal using various modern surgical techniques. The hospital mortality rate was 2.7%.

A clinically compatible in vitro drug-screening platform identifies therapeutic vulnerabilities in primary cultures of brain metastases.

PURPOSE: Brain metastases represent the most common intracranial tumors in adults and are associated with a poor prognosis. We used a personalized in vitro drug screening approach to characterize individual therapeutic vulnerabilities in brain metastases. METHODS: Short-term cultures of cancer cells isolated from brain metastasis patients were molecularly characterized using next-generation sequencing and functionally evaluated using high-throughput in vitro drug screening to characterize pharmacological treatment sensitivities. RESULTS: Next-generation sequencing identified matched genetic alterations in brain metastasis tissue samples and corresponding short-term cultures, suggesting that short-term cultures of brain metastases are suitable models for recapitulating the genetic profile of brain metastases that may determine their sensitivity to anti-cancer drugs. Employing a high-throughput in vitro drug screening platform, we successfully screened the cultures of five brain metastases for response to 267 anticancer compounds and related drug response to genetic data. Among others, we found that targeted treatment with JAK3, HER2, or FGFR3 inhibitors showed anti-cancer effects in individual brain metastasis cultures. CONCLUSION: Our preclinical study provides a proof-of-concept for combining molecular profiling with in vitro drug screening for predictive evaluation of therapeutic vulnerabilities in brain metastasis patients. This approach could advance the use of patient-derived cancer cells in clinical practice and might eventually facilitate decision-making for personalized drug treatment.

Combined use of 3D printing and mixed reality technology for neurosurgical training: getting ready for brain surgery.

OBJECTIVE: Learning surgical skills is an essential part of neurosurgical training. Ideally, these skills are acquired to a sufficient extent in an ex vivo setting. The authors previously described an in vitro brain tumor model, consisting of a cadaveric animal brain injected with fluorescent agar-agar, for acquiring a wide range of basic neuro-oncological skills. This model focused on haptic skills such as safe tissue ablation technique and the training of fluorescence-based resection. As important didactical technologies such as mixed reality and 3D printing become more readily available, the authors developed a readily available training model that integrates the haptic aspects into a mixed reality setup. METHODS: The anatomical structures of a brain tumor patient were segmented from medical imaging data to create a digital twin of the case. Bony structures were 3D printed and combined with the in vitro brain tumor model. The segmented structures were visualized in mixed reality headsets, and the congruence of the printed and the virtual objects allowed them to be spatially superimposed. In this way, users of the system were able to train on the entire treatment process from surgery planning to instrument preparation and execution of the surgery. RESULTS: Mixed reality visualization in the joint model facilitated model (patient) positioning as well as craniotomy and the extent of resection planning respecting case-dependent specifications. The advanced physical model allowed brain tumor surgery training including skin incision; craniotomy; dural opening; fluorescence-guided tumor resection; and dura, bone, and skin closure. CONCLUSIONS: Combining mixed reality visualization with the corresponding 3D printed physical hands-on model allowed advanced training of sequential brain tumor resection skills. Three-dimensional printing technology facilitates the production of a precise, reproducible, and worldwide accessible brain tumor surgery model. The described model for brain tumor resection advanced regarding important aspects of skills training for neurosurgical residents (e.g., locating the lesion, head position planning, skull trepanation, dura opening, tissue ablation techniques, fluorescence-guided resection, and closure). Mixed reality enriches the model with important structures that are difficult to model (e.g., vessels and fiber tracts) and advanced interaction concepts (e.g., craniotomy simulations). Finally, this concept demonstrates a bridging technology toward intraoperative application of mixed reality.

Development and Validation of the Questionnaire of Young People's Participation-Young Adults (QYPP-YA).

BACKGROUND: The Questionnaire of Young People's Participation (QYPP) was developed for use in children and adolescents. To track participation throughout transition from childhood to adulthood, we adapted it for young adults using focus groups. Aim of this study was to validate this measure, the QYPP-Young Adults (QYPP-YA). METHODS: We recruited young adults with cerebral palsy (CP) and a representative, same-aged sample of the general population (GP). The GP-sample was split into two equivalent subsamples, one part to identify the factor structure via exploratory factor analysis and another part to test the resulting model via confirmatory factor analysis. Reliability and different forms of validity were investigated. RESULTS: The final QYPP-YA includes 17 items assigned to six domains (Autonomy, Independency, Intimate Relationships, Interpersonal Relationships, Social Life, Online Communication). Scales show satisfying internal consistencies in the CP-sample and in the GP-sample, except for 'Online Communication'. Convergent, divergent and known-group validity were confirmed. CONCLUSIONS: The QYPP-YA instrument features promising psychometric characteristics to assess key domains of participation in healthy and disabled young adults. It provides a multidimensional, economic and sound assessment for use in population surveys and clinical trials.

The impact of preoperative MRI-based apparent diffusion coefficients on local recurrence and outcome in patients with cerebral metastases.

BACKGROUND: Surgery of single cerebral metastases is standard but frequently fails to achieve local tumour control. Reliable predictors for local tumour progression and overall survival are unknown. MRI-based apparent diffusion coefficients (ADC) correlate with tumour cellularity and invasion. The present study analysed a potential relation between the MRI based apparent diffusion coefficients local recurrence and outcome in patients with brain metastases. METHODS: A retrospective analysis was performed for patients with cerebral metastases and complete surgical resection evaluated by an early postoperative MRI < 72h. Minimal ADC and mean ADC were assessed in preoperative 1,5T-MRI scans by placing regions of interests in the tumour and the peritumoural tissue. RESULTS: Analysis of the relation between ADC values, local progression and outcome was performed in 86 patients with a mean age of 59 years (range 33-83 years). Primary site was NSCLC in 37.2% of all cases. Despite complete resection 33.7% of all patients suffered from local in-brain-progression. There were no significant differences in ADC values in groups based on histology. In the present cohort, the mean ADCmin and the mean ADCmean within the metastasis did not differ significantly between patients with and without a later local in-brain progression (634 × 10-6 vs. 661 × 10-6 mm2/s and 1324 × 10-6 vs. 1361 × 10-6 mm2/s; 1100 × 10-6 vs. 1054 × 10-6 mm2/s; each p > 0.05). Mean ADC values did not correlate significantly with PFS and OAS. CONCLUSION: In the present study analysed ADC values had no significant impact on local in brain progression and survival parameters.

Masculinizing surgery in disorders/differences of sex development: clinician- and participant-evaluated appearance and function.

OBJECTIVES: To report the long-term follow-up outcomes of masculinizing surgery in disorders/differences of sex development (DSD), including both physicians' and patients' perspectives on appearance and functional outcome, including sexuality. PATIENTS AND METHODS: In total, 1040 adolescents (age ≥16 years) and adults with a DSD took part in this multicentre cross-sectional clinical study in six European countries in 2014/2015. Of those, 150 living in other than the female gender had some kind of masculinizing surgery: hypospadias repair, orchidopexy, breast reduction and/or gonadectomy. The study protocol included medical data collection, an optional genital examination, and patient-reported outcomes including satisfaction with appearance and current sexual functioning. RESULTS: Diagnoses included partial and mixed gonadal dysgenesis (45,XO/46,XY; n = 38), Klinefelter syndrome/46,XX males (n = 57), and various 46,XY DSDs (n = 42; e.g. partial androgen insensitivity syndrome, severe hypospadias) and 13 with other diagnoses. Of the participants, 84 underwent hypospadias surgery, 86 orchidopexy, 52 gonadectomy and 32 breast reduction (combinations possible). Physicians evaluated anatomical appearance at genital examination as poor in approximately 11% of patients. After hypospadias surgery, 38% of participants reported that they were (very) dissatisfied with anatomical appearance and 20% with function. The physician and patient evaluations were moderately correlated (r = 0.43). CONCLUSION: The majority of participants were neutral to satisfied with the appearance and function in the long-term after masculinizing surgery. Given the initial severe phenotype and a risk of unsatisfactory results after masculinizing surgery in DSD, treatment should be handled by experienced multidisciplinary teams in order to optimize the postoperative results.

Quality of life and mental health in emerging adults with cerebral palsy compared to the general population.

BACKGROUND: While evidence concerning Quality of Life (QoL) in youth with cerebral palsy (CP) in comparison to the general population has been accumulating, there is a lack of studies exploring differences on a wider range of positive and negative mental health outcomes in emerging adults. METHODS: This binational case control study is part of the SPARCLE cohort study on QoL and participation of youth with CP. QoL (WHOQOL-BREF), depression (PHQ-9), anxiety (GAD-7) and self-efficacy (GSE) were assessed in 198 emerging adults with CP and 593 emerging adults from the general population, matched for country of residence, age and gender. ANCOVAs with impairment and pain as covariates were run. RESULTS: Similar levels of QoL were found in both samples, except for the environmental domain, with better QoL for emerging adults with CP compared to the general population. There were significant descriptive differences regarding depression with worse levels in the CP sample, however, also worse levels of self-efficacy. Pain as a covariate had a significant negative impact on all measures, leading to poorer self-efficacy while worsening depression and anxiety; impairment had a significant worsening impact on physical QoL and self-efficacy only. CONCLUSION: Similar expressions of mental health outcomes in emerging adults with CP and the general population indicate the high adaptive capability of emerging adults with CP.

Would they do it again? Final treatment decisions in malignant brain tumour patients-a caregiver's perspective.

PURPOSE: Overall survival of malignant brain tumour patients has significantly been increased over the last years. However, therapy remains palliative, and side effects should be balanced. Once terminal phase is entered, both patients and caregivers may find it hard to accept, and further therapies are demanded. But little is known about this highly sensitive period. Therefore, we analysed the last therapy decisions from the family caregiver's perspective. Would they support their beloved ones in the same way or would they now recommend a different therapy decision? METHODS: Caregivers of deceased malignant brain tumour patients, treated at our neurooncological centre between 2011 and 2017, were included. We designed a questionnaire to analyse the impact of the last therapy decision (resection, chemotherapy, radiotherapy), focusing on probable repeat of the choice taken and general therapy satisfaction. Independent variables, for example "satisfaction with therapy", were analysed using linear regression analysis, the coefficient of determination R2 and the standardized regression coefficient ß. The binary logistic regression analyses were taken to illustrate relationships with the dichotomously scaled outcome parameter "re-choice of therapy". Odds ratio analyses were used to determine the strength of a relationship between two characteristics. RESULTS: Data from 102 caregivers (life partners (70.6%)) were analysed retrospectively. Each 40% of patients died in a hospice or at home (20% in a hospital). In 67.6% the last therapy was chemotherapy followed by radiotherapy (16.7%) and surgery (15.7%). A positive evaluation of the last therapy was significantly correlated to re-choosing of respective therapy (chemo-/radiotherapy: p = 0.000) and satisfaction with informed consent (p = 0.000). Satisfaction regarding interpersonal contact was significantly correlated to satisfaction with resection (p = 0.000) and chemotherapy (p = 0.000 27 caregivers (28.7%) felt overburdened with this situation). CONCLUSION: This analysis demonstrates a significant correlation between a positive relation of patient/caregiver/physician and the subjective perception of the latest therapy. It underlines the central role of caregivers, who should be involved in therapy discussions. Neurooncologists should be specially trained in communication and psycho-oncology.

Synthetic vascular grafts as a new treatment option for space-occupying tumor bed cysts.

INTRODUCTION: Several authors have reported the formation of slit valves as the underlying pathomechanism of space-occupying tumor bed cysts. Iatrogenic slit valves following the resection of high-grade gliomas have been linked to certain risk factors such as intraoperative opening of the ventricles and attempts to seal these. The best therapeutic management of such cystic lesions remains elusive. Several treatment options such as cyst fenestration or cystoperitoneal shunting have been employed but remain associated with high rates of recurrence. With the given complications of the above-described treatment options, the objective was to devise a new therapy option that is safe and effective and treats the slit valve itself rather than its symptoms. METHODS: Between the years of 2010 and 2020, we successfully treated four patients with high-pressure tumor bed cysts following glioma resection by implantation of synthetic ringed vascular grafts into the slit valve. RESULTS: Postoperatively, the tumor bed cysts were regressive in all patients. Moreover, none of the treatment patients developed any complications associated with the implanted vascular grafts. Revision-free survival was 10, 12, 53, and 126 months, respectively. CONCLUSION: The use of synthetic vascular grafts as a means of stenting slit valves is a safe and effective novel treatment option for high-pressure tumor bed cysts.

Psychooncological distress in low-grade glioma patients-a monocentric study.

BACKGROUND: Patients diagnosed with low-grade glioma (LGG) must live with constant knowledge of an upcoming malignant tumor transformation which may lead to increased anxiety and reduced quality of life. Here, we (1) analyzed the prevalence and risk factors for distress in LGG patients using (2) different screening tools to subsequently (3) evaluate their need for psychological support. METHOD: Patients with LGG-suspicious findings in MRI studies as well as patients with histopathological confirmed LGG were screened using three established self-assessment instruments (Hospital Anxiety and Depression Scale, Distress Thermometer, EORTC-QLQ-C30-BN20). Screening results were correlated with sociodemographic factors. RESULTS: One hundred forty-nine patients (74 men and 75 women) were prospectively included. Patients were further divided into different subgroups regarding the time of screening and diagnosis. An increased level of distress was observed in 20.8% (mean score 1.21, 95% CI 1.15-1.28) of all patients screened by HADS. Significant associated factors were pre-existing psychiatric disorders (p = 0.003) and psychotropic medication (p = 0.029). HRQoL (p = 0.022) and global health item (p = 0.015), as well as future uncertainty (p = 0.047), assessed by the EORTC-QLQ-C30-BN20 were significantly higher in those patients without histopathological diagnosis. Increased distress was significantly correlated with results in chosen sub-items of the HRQoL questionnaire (p < 0.001). CONCLUSIONS: Our results demonstrate the need for frequent distress screening. If specific tools are not available, HRQoL questionnaires can also be used. Patients with pre-existing psychological stress should be offered additional psychooncological support, irrespectively of the time of screening or tumor diagnosis. CLINICAL TRIAL REGISTRATION NUMBER: 4087.

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.

Determinants of participation and quality of life of young adults with cerebral palsy: longitudinal approach and comparison with the general population - SPARCLE 3 study protocol.

BACKGROUND: Effective inclusion in society for young people with disabilities is increasingly seen as generating opportunities for self-development, and improving well-being. However, significant barriers remain in the vast majority of activities meaningful for young adults. Research argues that various personal (disabilities, health) and environmental (access to the resources needed, accessible environment, discrimination, lack of personal economic independence) factors contribute to limited participation. However, previous studies conducted in young people with cerebral palsy (CP) mainly investigated the transition period to adulthood, and did not fully consider the whole range of impairment severity profiles or environmental barriers. In this study, we will use the follow-up of the SPARCLE cohort and a comparison group from the general population (1) to investigate the impact of the environment on participation and quality of life of young adults with CP, (2) to determine predictors of a successful young adulthood in educational, professional, health and social fields, (3) to compare quality of life and frequency of participation in social, work and recreational activities with the general population, (4) to document on participation and quality of life in those with severe disabilities. METHODS: The SPARCLE3 study has a combined longitudinal and cross-sectional design. Young adults with CP aged 22 to 27 years in 6 European regions previously enrolled in the SPARCLE cohort or newly recruited will be invited to self-complete a comprehensive set of questionnaires exploring participation (daily life and discretionary activities), health-related quality of life, body function, personal factors (health, personal resources), and contextual factors (availability of needed environmental items, family environment, services provision) during home visits supervised by trained researchers. Proxy-reports or adapted questionnaires will be used for those with the most severe impairments. The recruitment of a large group from the general population (online survey) will enable to identify life areas where the discrepancies between young people with CP and their able-bodied peers are the most significant. DISCUSSION: This study will help identify to what extent disabilities and barriers in environment negatively affect participation and quality of life, and how previous valued experiences during childhood or adolescence might modulate these effects.

Disparity of child/parent-reported quality of life in cerebral palsy persists into adolescence.

AIM: To examine the evolution of child-parent discrepancy in reporting quality of life (QoL) between childhood and adolescence in children with cerebral palsy (CP) and to investigate potential factors associated with such a discrepancy. METHOD: We used data from the SPARCLE (Study of PARticipation of Children with CP Living in Europe) study, a population-based cohort study of children with CP, aged 8 to 12 years at baseline (in 2004-2005), in nine European centres, who were followed up at the age of 13 to 17 years. The KIDSCREEN-52 Quality of Life measure was used at baseline and follow-up; 354 child-parent dyads out of 500 eligible dyads were followed up (201 males, 153 females). We used intraclass correlation coefficients (ICCs) to examine agreement between parent proxy-reports and self-reported QoL. We used linear regression to examine factors associated with child-parent discrepancy in QoL reporting. RESULTS: Agreement was low to moderate (ICC=0.16-0.48) in childhood and in adolescence across all QoL domains. In four domains (moods and emotions, self-perception, relationship with parents and home life, and social support and peers), the extent of the discrepancy increased significantly between childhood and adolescence. Parenting stress, child pain, and child behaviour problems influenced parent proxy-reports during both childhood and adolescence. INTERPRETATION: The points of view of the child and their parents should be treated as complementary to obtain better knowledge regarding the QoL of children and adolescents with CP.

Early Genital Surgery in Disorders/Differences of Sex Development: Patients' Perspectives.

Controversy continues over a proposed moratorium on elective genital surgery in childhood for disorders/differences of sex development (DSD). Empirical evidence on patient preference is needed to inform decision-making. We conducted a multicentre survey by cross-sectional questionnaire in 14 specialized clinics in six European countries. The sample comprised 459 individuals (≥ 16 years) with a DSD diagnosis, including individuals with congenital adrenal hyperplasia (CAH) (n = 192), XY DSD with prenatal androgen effect (A) (n = 150), and without (nA) (n = 117). Main outcome measures were level of agreement with given statements regarding genital surgery, including clitoris reduction, vaginoplasty, and hypospadias repair. A total of 66% of individuals with CAH and 60% of those with XY DSD-A thought that infancy or childhood were the appropriate age for genital surgery. Females with XY DSD were divided on this issue and tended to prefer vaginoplasty at a later age (XY DSD-A 39%, XY DSD-nA 32%). A total of 47% of males preferred early hypospadias surgery. Only 12% (CAH), 11% (XY DSD-A), and 21% (XY DSD-nA) thought they would have been better off without any surgery in childhood or adolescence. Individuals who had early genital surgery were more likely to approve of it. Outcome data failed to support a general moratorium on early elective genital surgery. Participant perspectives varied considerably by diagnostic category, gender, history of surgery, and contact with support groups. Case-by-case decision-making is better suited to grasping the ethical complexity of the issues at stake.Trial registration: German Clinical Trials Register DRKS00006072.

Diagnostic impact of additional O-(2-[18F]fluoroethyl)-L-tyrosine (18F-FET) PET following immunotherapy with dendritic cell vaccination in glioblastoma patients.

OBJECTIVE: Vaccination therapy using tumour antigen-loaded, autologous dendritic cells (DC) is a promising therapeutic approach alongside standard treatment for glioblastoma (GBM). However, reliable diagnostic criteria regarding therapy monitoring are not established. Here, we analysed the impact of additional 18F-fluoroethyl-tyrosine positron emission tomography (18F-FET PET) imaging following DC vaccination therapy. METHODS: We analysed data of GBM patients who received DC vaccination therapy. Following MRI diagnosis of tumour recurrence, additional static and dynamic 18F-FET PET imaging was performed. Vaccination was performed five times by intradermal injections, either weekly between concomitant radio/-chemotherapy and intermittent chemotherapy or after tumour recurrence, before re-radiation therapy. MRI and 18F-FET PET results were compared and correlated with clinical data. RESULTS: Between 2003 and 2016, 5 patients were identified who received DC vaccination and 18F-FET PET imaging (1 female/4 males; mean age: 44 ± 14 y). 3/5 patients showed congruent results of tumour progression. In three patients 18F-FET PET indicated treatment related changes, which was in contrast to MRI findings that indicated tumour progression. In these patients 18F-FET PET results could be confirmed by either neuropathological diagnosis or according to the RANO criteria. CONCLUSIONS: Despite the small patients number our results indicate an additional impact of 18F-FET PET for monitoring outcome following vaccination therapy.

Prediction of survival in patients with IDH-wildtype astrocytic gliomas using dynamic O-(2-[18F]-fluoroethyl)-L-tyrosine PET.

PURPOSE: Integrated histomolecular diagnostics of gliomas according to the World Health Organization (WHO) classification of 2016 has refined diagnostic accuracy and prediction of prognosis. This study aimed at exploring the prognostic value of dynamic O-(2-[18F]-fluoroethyl)-L-tyrosine (FET) PET in newly diagnosed, histomolecularly classified astrocytic gliomas of WHO grades III or IV. METHODS: Before initiation of treatment, dynamic FET PET imaging was performed in patients with newly diagnosed glioblastoma (GBM) and anaplastic astrocytoma (AA). Static FET PET parameters such as maximum and mean tumour/brain ratios (TBRmax/mean), the metabolic tumour volume (MTV) as well as the dynamic FET PET parameters time-to-peak (TTP) and slope, were obtained. The predictive ability of FET PET parameters was evaluated concerning the progression-free and overall survival (PFS, OS). Using ROC analyses, threshold values for FET PET parameters were obtained. Subsequently, univariate Kaplan-Meier and multivariate Cox regression survival analyses were performed to assess the predictive power of these parameters for survival. RESULTS: Sixty patients (45 GBM and 15 AA patients) of two university centres were retrospectively identified. Patients with isocitrate dehydrogenase (IDH)-mutant or O6-methylguanine-DNA-methyltransferase (MGMT) promoter-methylated tumours had a significantly longer PFS and OS (both P < 0.001). Furthermore, ROC analysis of IDH-wildtype glioma patients (n = 45) revealed that a TTP > 25 min (AUC, 0.90; sensitivity, 90%; specificity, 87%; P < 0.001) was highly prognostic for longer PFS (13 vs. 7 months; P = 0.005) and OS (29 vs. 12 months; P < 0.001). In contrast, at a lower level of significance, TBRmax, TBRmean, and MTV were only prognostic for longer OS (P = 0.004, P = 0.038, and P = 0.048, respectively). Besides complete resection and a methylated MGMT promoter, TTP remained significant in multivariate survival analysis (all P ≤ 0.02), indicating an independent predictor for OS. CONCLUSIONS: Our data suggest that dynamic FET PET allows the identification of patients with longer OS among patients with newly diagnosed IDH-wildtype GBM and AA.

Determination of optimal time window for cortical mapping in awake craniotomy: assessment of intraoperative reaction speed.

Currently, there is no known time frame when the patients are the most responsive during awake craniotomy. The aim of this work is therefore to determine when the patient has the shortest reaction time and so to extrapolate the optimal time window for cortical mapping. In this analytic observational study, our group has recorded the reaction times of 35 patients undergoing an awake craniotomy and compared them with the preoperative baseline. The operations were performed according to a "sleep-awake-awake" protocol. Data collection was performed in parallel with standard methods for evaluation of language and cognitive functions. The preoperative reaction times of our patient cohort (average ± SD = 510 ± 124 ms) were significantly shorter than those measured during the operation 786 ± 280 ms, p < .001. A one-factor ANOVA within subjects showed a significant increase in reaction times; p < .001. Post hoc comparisons on a Bonferroni-corrected α-error level of .05 showed significant differences between the reaction speed during the 0-10 min time frame and the preoperative baseline, as well as the intraoperative reaction times during the 20-30 min, 30-40 min, and the t > 40 min time frames. In conclusion, measurement of intraoperative reaction speed seems to be a technically feasible method that is well tolerated by the patients. The intraoperative reaction speed performance was shown to be significantly slower than on the day before the operation. The patients seem to be the slowest directly after extubation and gradually wake up during the awake phase. The poorest wakefulness is demonstrated during the first 20 min after extubation.

AI Approaches Towards Prechtl's Assessment of General Movements: A Systematic Literature Review.

General movements (GMs) are spontaneous movements of infants up to five months post-term involving the whole body varying in sequence, speed, and amplitude. The assessment of GMs has shown its importance for identifying infants at risk for neuromotor deficits, especially for the detection of cerebral palsy. As the assessment is based on videos of the infant that are rated by trained professionals, the method is time-consuming and expensive. Therefore, approaches based on Artificial Intelligence have gained significantly increased attention in the last years. In this article, we systematically analyze and discuss the main design features of all existing technological approaches seeking to transfer the Prechtl's assessment of general movements from an individual visual perception to computer-based analysis. After identifying their shared shortcomings, we explain the methodological reasons for their limited practical performance and classification rates. As a conclusion of our literature study, we conceptually propose a methodological solution to the defined problem based on the groundbreaking innovation in the area of Deep Learning.

Mental Health of a Large Group of Adults With Disorders of Sex Development in Six European Countries.

OBJECTIVE: The aim of the study was to evaluate psychiatric symptoms among 1022 persons with various disorders of sex development (DSDs). METHODS: The study was a European multicenter cross-sectional clinical evaluation in six countries. The mean (SD) age of participants was 32.1 (13.4) years. The cohort consisted of 325 individuals with Turner syndrome, 219 individuals with Klinefelter syndrome (KS), female individuals with various XY-DSD conditions (107 with and 67 without androgenization), 87 male individuals with XY-DSD conditions, and 221 female individuals with congenital adrenal hyperplasia. The Hospital Anxiety and Depression Scale, the Short Autism Spectrum Quotient, the Adult Attention-Deficit/Hyperactivity Disorder Self-Report Scale, and self-reported mental health history were used to assess psychiatric symptoms. RESULTS: Across the six DSD diagnostic groups, clinical cutoff symptom scores were reached in 19.5% of participants for anxiety, in 7.1% for depression, in 4.1% for attention-deficit/hyperactivity disorder, and in 9.1% for autism. The mean depression and anxiety scores were higher compared with population norms in men with KS and men with XY-DSD. Compared with participants with other DSD conditions, men with KS reported significantly more mental health symptoms. Self-esteem, satisfaction with care, body dissatisfaction, and experiences of shame were associated with psychiatric symptoms in many DSD conditions. CONCLUSIONS: A substantial minority of adults with DSD, with KS in particular, experience psychiatric morbidity. Across DSD conditions, adults may share feelings of shame. Developing a positive self-esteem and body image may be challenging. Multidisciplinary DSD care that involves specialized mental health support can be of important value. TRIAL REGISTRATION: German Clinical Trials Register DRKS00006072.

Is 5-ALA fluorescence of cerebral metastases a prognostic factor for local recurrence and overall survival?

BACKGROUND: 5-Aminolevulinic acid (5-ALA) fluorescence-guided resection technique was first introduced for malignant glioma. However, the impact of the 5-ALA fluorescence behaviour of cerebral metastases is still unclear. Aim of this study was to determine the impact of PpIX-fluorescence on the local progression-free and overall survival. MATERIALS AND METHODS: A secondary analysis was performed and included an updated follow-up of 136 patients comprised in two previous studies. Additionally, 82 new patients were included. All patients underwent surgical resection of cerebral metastasis and intraoperative estimation of 5-ALA-induced fluorescence. The 5-ALA fluorescence behaviour of cerebral metastases was correlated with the rate of local recurrences, the local progression-free and overall survival. RESULTS: 218 patients suffering from cerebral metastatic spread fulfilled the inclusion criteria and were analysed: complete surgical resection could be achieved in 123/218 patients (56.4%). Dichotomised degree of surgical resection (complete vs. incomplete or questionable complete resection) was not related to dichotomized 5-ALA fluorescence of cerebral metastases (p = 0.66). 51 patients (23.4%) developed a local in-brain progression within or at the border of the resection cavity. Of these, 8 patients showed a PpIX-fluorescent metastasis. There was a trend towards a correlation between a higher local in-brain progression in PpIX-non-fluorescent metastases (p = 0.03). Median time to local in-brain progression was 4 ± 11 months. PpIX-fluorescent and PpIX-non-fluorescent metastases showed a significantly different progression-free survival (p = 0.01). PpIX-positive and -negative metastases showed a significantly different overall survival (20 and 14 months respectively; p = 0.006). CONCLUSION: The 5-ALA fluorescence behaviour was related to the local progression-free and the overall survival in the present retrospective series and might be considered a prognostic marker. Further studies are required to appreciate the oncological impact of the 5-ALA induced fluorescence behaviour of cerebral metastases.